INVITED ORAL PRESENTATIONS

. 2018 Sep;7(Suppl 1):S1–S48.

INVITED ORAL PRESENTATIONS

PMCID: PMC6231293

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Cardiology: What’s Best for Women in 2018?

Cardiovascular disease continues to be the first cause of death in Australian women and worldwide.[1] Cardiovascular outcomes are worse in women than men, and this is due to a constellation of factors which include phonotypical and pathophysiological differences, more challenging clinical presentation with “atypical” symptoms, delays in diagnosis, treatment and less aggressive management that their counterpart males.[2]

Women have traditionally been significantly underrepresented in clinical trials, and hence management has historically been based on extrapolation of results of trials conducted largely in men. Hence, determining the cause of the poorer outcomes in females has been elusive. Current knowledge supports anatomical and pathophysiological differences that influence the presentation of coronary artery disease in females, including more non-obstructive coronary artery disease, higher rates of plaque erosion and microvascular dysfunction, and less obstructive coronary artery disease than their counterpart males.[3,4,5]

Contemporary imaging approaches based on the current knowledge on sex- specific aspects of cardiovascular disease will be discussed, including the role of newer techniques on cardiac catheterization and non-invasive imaging modalities that have a significant role in the current management of cardiovascular diseases in women.

References

1.Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics–2015 update: A report from the American Heart Association. Circulation. 2015;131:e29–322. doi: 10.1161/CIR.0000000000000152. [DOI] [PubMed] [Google Scholar]
2.Wilmot KA, O'Flaherty M, Capewell S, Ford ES, Vaccarino V. Coronary heart disease mortality declines in the United States from 1979 through 2011: Evidence for stagnation in young adults, especially women. Circulation. 2015;132:997–1002. doi: 10.1161/CIRCULATIONAHA.115.015293. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Shaw LJ, Kohli P, Chandrashekhar Y, Narula J. Cardiovascular imaging of women: We have come a long way but still have a ways to go. JACC Cardiovasc Imaging. 2016;9:502–3. doi: 10.1016/j.jcmg.2016.02.012. [DOI] [PubMed] [Google Scholar]
4.Schulman-Marcus J, Hartaigh BÓ, Gransar H, Lin F, Valenti V, Cho I, et al. Sex-specific associations between coronary artery plaque extent and risk of major adverse cardiovascular events: The CONFIRM long-term registry. JACC Cardiovasc Imaging. 2016;9:364–72. doi: 10.1016/j.jcmg.2016.02.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Baldassarre LA, Raman SV, Min JK, Mieres JH, Gulati M, Wenger NK, et al. Noninvasive imaging to evaluate women with stable ischemic heart disease. JACC Cardiovasc Imaging. 2016;9:421–35. doi: 10.1016/j.jcmg.2016.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Anatomy versus Function Investigate Chest Pain

Barry Elison ¹

Anatomy utilizing non-invasive care will continue to replace and dominate functional assessment of chest pain.

In essence, the debate regarding function vs anatomy will continue for some time in the future. In the early phase of the emergence of CT coronary angiography as an investigation modality for coronary artery disease the criticisms of this modality were largely around lack of data with respect to accuracy, outcomes and its role in the algorithm of investigation of patients with chest pain for coronary artery disease and/or ischaemia. Furthermore, the modality was criticized for its lack of simplicity requiring substantial preparation techniques, high-end equipment and of course radiation dose. There has been a significant change in its utilization and acceptance in investigation of patients for coronary artery disease in the last decade.

In so far as the debate is concerned, the issues to be discussed will be:

Whether or not to add a calcium score to the investigation and what is the current state of the literature with respect to Calcium score.
Analysis of the some of the very important outcome based clinical trials that have been published particularly Promise and Scot Heart and some of the subsequent literature relating to these very important studies.
There have been some very important publications with respect to its role in functional imaging -particularly FFR-CT and I will outline some of these comparative studies with respect to FFR-CT.
Some prognostic findings within the study itself such as vulnerable plaque and their relevance.
A lot of the criticism for this modality was aimed at the hardware requirements, the presence or absence of Calcium and preparation.

The technological advances have made performance of this study far more simple. If time permits, there will be some discussion on new technology with respect to dual energy technology and signal rotation acquisitions.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Read with the Experts – Heart Failure and I-123 Meta-Iodobenzylguanidine

Kenichi Nakajima ¹

The aim is to understand the standardised approach for I-123 MIBG imaging and how to use I-123 MIBG for risk stratification.

I-123 meta-iodobenzylguanidine (MIBG) imaging is a unique methodology to visualize integrity of sympathetic nerve function. In patients with heart failure, I-123 MIBG myocardial uptake is a powerful indicator of prognosis, and quantitative parameter most widely used is a heart-to-mediastinum (H/M) ratio calculated by an anterior planar view.[1] However, the H/M ratio is known to be influenced by camera-collimator combinations including low-energy, low-medium-energy, and medium-energy collimators.[2,3] As we have advocated a phantom-based standardization method for H/M ratios, >2000 phantom experiments have been performed in Japan and 210 experiments were added in Europe.

At present H/M ratios calculated using any collimator conditions can be standardized. One of the most important applications of the standardized H/M ratio is to create mortality risk models including I-123 MIBG.[4] Two-year and 5-year mortality risk models were created with the combination of age, sex, H/M ratio, left ventricular ejection fraction and NYHA functional class. When the mortality risk model was validated in another cohort of patients, prediction of cardiac death was comparable to actual outcome in low-to-intermediate risk patients.[5] Tomographic images have also been used to evaluate regional distribution of MIBG, and semiquantitative scoring methods need normal databases and/or comparison with perfusion defects.

Standardized MIBG indices can be effectively used for risk stratification of patients with heart failure.

Disclosure of interest: K Nakajima - Conflict with Collaborative research with FUJIFILM RI Pharma.

References

1.Nakajima K, Nakata T. Cardiac 123I-MIBG imaging for clinical decision making: 22-year experience in Japan. J Nucl Med. 2015;56(Suppl 4):11S–9S. doi: 10.2967/jnumed.114.142794. [DOI] [PubMed] [Google Scholar]
2.Nakajima K, Okuda K, Yoshimura M, Matsuo S, Wakabayashi H, Imanishi Y, et al. Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-to-mediastinum ratios to overcome camera-collimator variations. J Nucl Cardiol. 2014;21:970–8. doi: 10.1007/s12350-014-9916-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Verschure DO, Poel E, Nakajima K, Okuda K, van Eck-Smit BL, Somsen GA, et al. A European myocardial 123I-mIBG cross-calibration phantom study. J Nucl Cardiol. 2017 Jan 24; doi: 10.1007/s12350-017-0782-6. doi: 10.1007/s12350-017-0782-6. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Nakajima K, Nakata T, Matsuo S, Jacobson AF. Creation of mortality risk charts using 123I meta-iodobenzylguanidine heart-to-mediastinum ratio in patients with heart failure: 2- and 5-year risk models. Eur Heart J Cardiovasc Imaging. 2016;17:1138–45. doi: 10.1093/ehjci/jev322. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Nakajima K, Nakata T, Doi T, Kadokami T, Matsuo S, Konno T, et al. Validation of 2-year 123I-meta-iodobenzylguanidine-based cardiac mortality risk model in chronic heart failure. Eur Heart J Cardiovasc Imaging. 2018;19:749–56. doi: 10.1093/ehjci/jey016. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Current Status and Local Challenges in Asia

Kenichi Nakajima ¹

The aim of this presentation is to understand the need for population-specific databases, and evidence-based approach in Japan and Asia.

Nuclear cardiology is recognized as an important tool for the diagnosis of coronary artery disease. Although the role of myocardial perfusion imaging (MPI) is well known there are still variations for the use of nuclear cardiology among Asian countries; Japan, Korea, Taiwan, Singapore, and other countries. After the advent of coronary computed-tomography angiography, number of MPI is stable or slightly decreasing depending on countries.

Since most of large-scale nuclear medicine databases for diagnosis and prognosis have been accumulated in the United States, nuclear databases fitted for Asian populations is indispensable. In Japan, normal SPECT databases are created by Japanese Society of Nuclear Medicine working group for MPI (²⁰¹Tl, ^99mTc-MIBI/tetrofosmin), fatty acid imaging with ¹²³I-BMIPP and sympathetic nerve imaging with ¹²³I-MIBG.[1,2]

Prognosis of the patients with coronary artery disease should also be based on Asian databases. In Japan, J-ACCESS multi-center prognostic studies confirmed importance of MPI.[3,4] Based on the multivariate analysis of the Japanese database, risk model for predicting major cardiac events were created. In addition, patient background information such as diabetes and chronic kidney disease is important factors that affect major cardiac events.

Sympathetic imaging with ¹²³I-MIBG has been used in patients with heart failure, which is approved by Japanese Circulation Society’s guidelines. While threshold value of heart-to-mediastinum ratio (H/M) has been proposed by ADMIRE-HF study, we have created multivariate mortality risk model including standardized MIBG H/M,[5,6] and the accuracy was confirmed by an additional cohort of heart-failure patients.

Population-specific approaches and databases are important for diagnosis and prognosis in Asian countries, which enable effective risk stratification of the patients with heart diseases.

Disclosure of interest: K Nakajima - Conflict with FUJIFILM RI Pharma, Nihon Medi-physics.

References

1.Nakajima K. Normal values for nuclear cardiology. Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function. Ann Nucl Med. 2010;24:125–35. doi: 10.1007/s12149-009-0337-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Nakajima K. J-ACCESS review article and risk model. Ann Nucl Med. 2016;30:1882. [Google Scholar]
3.Nakajima K, Nishimura T. Cardiovascular events in Japan. Lessons from the J-ACCESS multicenter prognostic study using myocardial perfusion imaging. Circ J. 2012;76:1313–21. doi: 10.1253/circj.cj-12-0260. [DOI] [PubMed] [Google Scholar]
4.Nakajima K, Matsuo S, Okuyama C, Hatta T, Tsukamoto K, Nishimura S, et al. Cardiac event risk in Japanese subjects estimated using gated myocardial perfusion imaging, in conjunction with diabetes mellitus and chronic kidney disease. Circ J. 2012;76:168–75. doi: 10.1253/circj.cj-11-0857. [DOI] [PubMed] [Google Scholar]
5.Nakajima K, Nakata T, Yamada T, Yamashina S, Momose M, Kasama S, et al. A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging. Eur J Nucl Med Mol Imaging. 2014;41:1673–82. doi: 10.1007/s00259-014-2759-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Nakajima K, Nakata T, Matsuo S, Jacobson AF. Creation of mortality risk charts using 123I meta-iodobenzylguanidine heart-to-mediastinum ratio in patients with heart failure: 2- and 5-year risk models. Eur Heart J Cardiovasc Imaging. 2016;17:1138–45. doi: 10.1093/ehjci/jev322. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Impact of Coronary Calcium Score as an Addition to Myocardial Perfusion Imaging in Altering Clinical Management

Stephen Stowers ¹

The use of visual estimation of coronary artery calcium (CAC) on hybrid SPECT/CT imaging can be to provide additional source of information to assist in the interpretation of borderline myocardial perfusion images (MPI). We assessed the effect of the absence of CAC on cardiac events and the interpretation of non-extensive perfusion defects in symptomatic patients.

At the time of MPI, hybrid systems obtain a low dose, non-ECG-gated CT scan that is used to perform attenuation correction. The utility of visual coronary CT attenuation correction scan (CTAC) in estimating actual CAC as measured by the Shemesh score (SS) was also validated. Six month phone interviews for cardiac events was conducted at six months on 30/150 patients whose CAC score was read as zero.

Visual assessment of CAC had a excellent intraclass correlation coefficient of 0.973 for total calcium score, with 95% confidence interval of 0.963 to 0.980. 20% (30/150) patients had a CAC score read as zero. 97% (29/30) MPI scans read with a CAC score of zero were also read as having no inducible myocardial perfusion abnormality despite 70% (21/30) having a abnormal SSS. 10% (3/30) patients had normal coronary angiography. No patient (0/30) had a cardiac event at six months whos CAC score was read as zero.

CAC can be visually estimated from a CTAC scan with high degree of inter-observer reproducibility. Absence of CAC influences the interpretation of borderline MPI and may better define the risk of cardiac events during follow-up.

References

1.Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR, Cavanaugh B, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372:1291–300. doi: 10.1056/NEJMoa1415516. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Einstein AJ, Johnson LL, Bokhari S, Son J, Thompson RC, Bateman TM, et al. Agreement of visual estimation of coronary artery calcium from low-dose CT attenuation correction scans in hybrid PET/CT and SPECT/CT with standard Agatston score. J Am Coll Cardiol. 2010;56:1914–21. doi: 10.1016/j.jacc.2010.05.057. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Chang SM, Nabi F, Xu J, Peterson LE, Achari A, Pratt CM, et al. The coronary artery calcium score and stress myocardial perfusion imaging provide independent and complementary prediction of cardiac risk. J Am Coll Cardiol. 2009;54:1872–82. doi: 10.1016/j.jacc.2009.05.071. [DOI] [PubMed] [Google Scholar]
4.Engbers EM, Timmer JR, Ottervanger JP, Mouden M, Knollema S, Jager PL, et al. Prognostic value of coronary artery calcium scoring in addition to single-photon emission computed tomographic myocardial perfusion imaging in symptomatic patients. Circ Cardiovasc Imaging. 2016;9:pii: e003966. doi: 10.1161/CIRCIMAGING.115.003966. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Endocrinology: What’s New in Adult Thyroid Cancer Management

Jeremy Hoang ¹

In the past few years, there has been major progress in our understanding and management of differentiated thyroid cancer. Significant advances are seen in the reclassification of the follicular variant of papillary thyroid cancer and the revision of the TNM classification coming into effect in 2018 that downstages many patients including those with nodal metastases.

Certain genetic mutations have been shown to be associated with worse prognosis and may be useful in the initial risk stratification. In the current era of tyrosine kinase inhibitors, the FDG PET and radioiodine scans are essential in verifying the presence of radioiodine refractory disease and help determine the disease burden and the rate of disease progression, factors that are crucial in guiding treatment.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Nuclear Medicine and Hyperparathyroidism

Ivan Ho Shon ¹

Primary hyperparathyroidism is an increasingly frequent diagnosis and definitive therapy is surgical resection of the overactive parathyroid gland(s). Minimally invasive para-thyroidectomy reduces operative time, morbidity and costs however requires accurate preoperative imaging localisation of the abnormal parathyroid gland(s). This presentation will review nuclear medicine techniques and other modalities for preoperative localisation of overactive parathyroid glands.

Parathyroid imaging with Tc-99m sestamibi has demonstrated high sensitivity and positive predictive value in the preoperative localisation of overactive parathyroid glands, particularly parathyroid adenomas. Positron emission tomography (PET) with methionine and more recently choline-based tracers have shown promising results and may be of benefit in patients where other studies are non-localising. In addition, there are several other modalities for localisation of overactive parathyroid glands, particularly ultrasound and multiphase x-ray computed tomography (CT) which have also demonstrated high sensitivity and positive predictive value in the preoperative localisation of parathyroid adenomas.

Imaging with Tc-99m sestamibi has an important role in primary hyperparathyroidism for the preoperative localisation of overactive parathyroid glands. There are a number of other effective imaging methods for preoperative localisation in hyperparathyroidism including PET, ultrasound and multiphase CT. All of these imaging techniques have complementary roles in imaging in primary hyperparathyroidism.

References

1.Bilezikian JP, Khan AA, Potts JT., Jr Third International Workshop on the Management of Asymptomatic Primary Hyperthyroidism. Guidelines for the management of asymptomatic primary hyperparathyroidism: Summary statement from the third international workshop. J Clin Endocrinol Metab. 2009;94:335–9. doi: 10.1210/jc.2008-1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14:115–25. doi: 10.1038/nrendo.2017.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, et al. The American Association of Endocrine Surgeons Guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151:959–68. doi: 10.1001/jamasurg.2016.2310. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Radioiodine in the Management of Benign Thyroid Disease: A Practical Australian Approach

W John McKay ¹

“The more things change the more they stay the same”. From a 45 year experience of managing patients with hyperthyroidism this presentation will discuss the changing trends in the management of patients with radioiodine over the years. The current international guidelines will be briefly discussed and a practical approach to the use of radioiodine in the management of benign thyroid disease will be suggested.

References

1.Lewitus Z, Lubin E, Rechnic J, Ben-Porath M, Feige Y. Treatment of thyrotoxicosis with 125-I and 131-I. Semin Nucl Med. 1971;1:411–21. doi: 10.1016/s0001-2998(71)81036-x. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

F-Fluoro-L-Dihydroxyphenylalnine Imaging in Hypoglycaemia of Infancy

David A Pattison ¹

Congenital hyperinsulinism (CHI) refers to a clinically, genetically and morphologically heterogenous condition associated with hypoglycaemia due to dysregulated insulin secretion. The hypoglycaemia can be persistent and severe, and prompt diagnosis and effective therapy is necessary to prevent complications including epilepsy, cerebral palsy and neurodevelopmental deficits.

Histologically CHI is classified in three subgroups: diffuse, focal and atypical forms. Diffuse disease affects all the islets in the pancreas, focal disease abnormality is confined to a small region of the pancreas, and atypical forms have also been described. Genetic analysis of different candidate genes (particularly ABCC8 and KCNJ11) is helpful in differentiating between these CHI subtypes. However, the introduction of ¹⁸F-fluoro-L-dihydroxyphenylalnine (¹⁸F-DOPA) PET/CT – based upon co-secretion of dopamine and insulin by human pancreatic beta cells – has led to a significant change in the diagnostic approach and therapy of CHI.

Treatment modalities for CHI include dietary modification, IV glucose infusion, medical therapy (primarily diazoxide and octreotide) and pancreatic surgery. Focal CHI is curable after focal enucleation, or partial pancreatectomy, without subsequent risk of diabetes or malabsorption. Surgery for diffuse CHI should be restricted to medical non-responders and ranges from partial to subtotal pancreatectomy. ¹⁸F-DOPA PET/CT imaging is less invasive and more accurate/reliable than previous techniques for identification and pre-operative localisation of pancreatic focal lesions to guide the surgical approach.[1] Localisation techniques include visual or quantitative methods, the latter using high standardised uptake value (SUV) ratio to identify the focal lesion with published SUV ratio cut-offs ranging between 1.2 to 1.5. Imaging protocols will be discussed and an approach to scan interpretation will be provided using case examples.

Reference

1.Otonkoski T, Näntö-Salonen K, Seppänen M, Veijola R, Huopio H, Hussain K, et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes. 2006;55:13–8. [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

SPECT/CT and PET/CT Imaging in Thyroid Cancer

Ka Kit Wong ¹

Well differentiated thyroid cancer (WDTC) incidence continues to increase due to earlier detection and environmental effects, with excellent prognosis for thyroid microcarcinoma and low-risk WDTC. Risk stratification based on histopathology, thyroglobulin measurement, and imaging guides management. The increase of the age threshold to 55 years in the 8^th edition of the AJCC TNM Staging for thyroid cancer will lead to downstaging compared to the prior edition. Radioiodine scintigraphy and fluorodeoxyglucose (FDG) PET/CT are complimentary imaging tests, providing insight into the biological behaviour of WDTC.

Hybrid SPECT/CT and PET/CT technology has achieved standard clinical usage. SPECT/CT provides incremental diagnostic value with well documented benefits over planar imaging on I-131 or I-123 scans. Pre-ablation diagnostic SPECT/CT reduces equivocal findings, allows for characterization of uptake as benign or malignant, and can detect unsuspected N1 or M1 disease. SPECT/CT can guide selection of I-131 activity dose for remnant ablation or targeting of radioiodine avid disease. Post therapy SPECT/CT completes staging of WDTC with the highest diagnostic sensitivity.

A wide spectrum of benign variants have been described on scintigraphy and SPECT/CT allows confident diagnosis of such false-positives. Dosimetry using SPECT-CT is possible though is currently under-utilized. The spectrum of WDTC ranges from classic types, Hürthle cell variants, high risk features (tall cell, columnar, etc.), to poorly differentiated thyroid cancer, with varying degrees of sodium iodide symporter (NIS) expression.

In the setting of elevated thyroglobulin and negative radioiodine scintigraphy, FDG PET/CT is useful for detection of structurally residual disease and performance can be augmented with rhTSH stimulation. Non-iodine-avid disease recurrence in the neck found on PET is amenable to surgical resection or ethanol ablation.

FDG PET/CT can also identify iodine refractory distant metastatic disease for which systemic multikinase inhibitor therapy is suitable. Positivity on PET imaging heralds a worst prognosis with 10-year survival falling to 50%.

Reference

1.Wong KK, Fig LM, Youssef E, Ferretti A, Rubello D, Gross MD, et al. Endocrine scintigraphy with hybrid SPECT/CT. Endocr Rev. 2014;35:717–46. doi: 10.1210/er.2013-1030. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Infection/Inflammation: Molecular Imaging in Diabetic Patients with Infection

Edel Noriega Álvarez, ISORBE ¹

Patients with longstanding diabetes develop peripheral neuropathy that, together with peripheral vascular disease (and microvascular dysfunction) often leads to foot complications that can affect the skin, soft tissues and bones. Up to 25% of the diabetic population is at risk of developing a pedal ulcer, frequently the cause of non-traumatic lower-extremity amputations that are associated with a 5-year mortality of approximately 50%.[1]

With clinical examination, it is difficult to differentiate between soft tissue infection and osteomyelitis (OM). Bone biopsy is an invasive procedure that loses its reliability when the fragment of the biopsy is contaminated by cutaneous bacteria.[2] Therefore, the image diagnosis is crucial in this evaluation.

Magnetic resonance imaging (MRI) is able to differentiate between OM and soft tissue infection,[3,4] but its specificity is reduced if there is bone destruction, dislocation, bone marrow oedema, synovial effusion and loss of margins of bone or joint, conditions that characterise neuroarthropathy and that it is difficult to differentiate from OM.

Molecular Imaging plays an important role in this clinical context. Bone scan (BS) is sensitive but not specific for OM in diabetic foot infection. Some researchers compare white blood cell labelled scan (WBC) versus the combination of BS + WBC, but combined study only shows a marginal improvement.[5] In a meta-analysis, WBC had a sensitivity and specificity of approximately 86% and 85%, respectively.[3] In another review, WBC sensitivity and specificity ranging between 79-100% and 70-97%, respectively, was reported.[6] Implementing in WBC scan the time decay corrected acquisition (TDCA), delayed planar images (8h or 24h) and SPECT/CT,[7] it is possible to differentiate OM versus Charcot arthropathy, but studies are still necessaries to confirm it.

¹⁸F-FDG PET is less sensitive but more specific than MRI for the diagnosis of bone involvement at 81% and 93% respectively, and 91% and 78% respectively.[6] A recent meta-analysis compares the four imaging modalities most commonly used in the diagnosis of OM of the diabetes foot (i.e., MRI, ¹¹¹In-oxine–WBC SPECT/CT, ^99mTc-HMPAO–WBC SPECT/CT, and ¹⁸F-FDG PET/CT). The authors suggest that ^99mTc-HMPAO–labelled WBC and ¹⁸F-FDG PET/CT offer the highest specificity for diagnosing OM while demonstrated comparable sensitivity to the other imaging techniques reviewed. Only 2 studies used a methodology proposed by European Association of Nuclear Medicine. In view of the continued lack of consensus on this issue, we believe there is a need for a standardization of diagnostic methods and an evidence-based sequential approach.[1]

No studies have yet been conducted with large series of patients comparing PET versus WBC with TDCA and delayed images. Therefore, WBC is currently the most widely used radionuclide study for the diagnosis of OM in diabetic foot.

References

1.Lauri C, Tamminga M, Glaudemans AW, Juárez Orozco LE, Erba PA, Jutte PC, et al. Detection of osteomyelitis in the diabetic foot by imaging techniques: A systematic review and meta-analysis comparing MRI, white blood cell scintigraphy, and FDG-PET. Diabetes Care. 2017;40:1111–20. doi: 10.2337/dc17-0532. [DOI] [PubMed] [Google Scholar]
2.Wheat LJ, Allen SD, Henry M, Kernek CB, Siders JA, Kuebler T, et al. Diabetic foot infections. Bacteriologic analysis. Arch Intern Med. 1986;146:1935–40. [PubMed] [Google Scholar]
3.Capriotti G, Chianelli M, Signore A. Nuclear medicine imaging of diabetic foot infection: Results of meta-analysis. Nucl Med Commun. 2006;27:757–64. doi: 10.1097/01.mnm.0000230065.85705.b3. [DOI] [PubMed] [Google Scholar]
4.Tomas MB, Patel M, Marwin SE, Palestro CJ. The diabetic foot. Br J Radiol. 2000;73:443–50. doi: 10.1259/bjr.73.868.10844873. [DOI] [PubMed] [Google Scholar]
5.Palestro CJ, Love C. Nuclear medicine and diabetic foot infections. Semin Nucl Med. 2009;39:52–65. doi: 10.1053/j.semnuclmed.2008.08.006. [DOI] [PubMed] [Google Scholar]
6.Israel O, Sconfienza LM, Lipsky BA. Diagnosing diabetic foot infection: The role of imaging and a proposed flow chart for assessment. Q J Nucl Med Mol Imaging. 2014;58:33–45. [PubMed] [Google Scholar]
7.Noriega-Álvarez E, Martínez Pimienta GA, Benítez Segura AM, Bajén Lázaro MT, Rodríguez-Gasén A, Rodríguez-Rubio Corona J, et al. Utility of 8h and time decay-corrected acquisition scintigraphy with in vitro labeled white blood cells for the diagnosis of osteoarticular infection. Nucl Med Commun. 2017;38:500–8. doi: 10.1097/MNM.0000000000000678. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging Fungal Infections

Alfred Ankrah ¹

There has been a steady increase in invasive fungal infections (IFIs) as a result of an increase in the immunocompromised population who are at risk for IFIs. IFIs cause significant morbidity and mortality in immunocompromised individuals, and early diagnosis, appropriate and optimal treatment are crucial for improving the outcome of IFIs. Imaging plays an essential role in the diagnosis, staging and therapy decision making in patients with IFIs. Imaging with ¹⁸F-FDG-PET/CT has been shown to be useful in IFI management. A high index of suspicion must be maintained when interpreting the PET/CT scans of the population at risk for IFIs. The most important role of ¹⁸F-FDG-PET appears to be its ability to monitor therapy in IFIs to determine the duration, the need to prolong the treatment, the need to switch the antifungal agent or even pursue a different therapeutic strategy such as surgical resection of the IFI lesion. Monitoring therapy with ¹⁸F-FDG-PET also enables the treatment for the underlying condition to be undertaken for the patient at an earlier point in time when other imaging modalities may not have shown a complete response to the antifungal therapy. ¹⁸F-FDG-PET is not without limitations, and the high tracer accumulation at physiologic sites may decrease lesion detectability. Again, the non-specificity of the ¹⁸F-FDG is particularly challenging in the immunocompromised patient. It is crucial to take all the relevant clinical data into account when interpreting the studies of patients at risk of or with known IFIs. Furthermore, the advantages and disadvantages of the other imaging modalities used in IFIs must be appreciated to optimize their use in IFIs. Some new tracers have yielded some promising results for the management of IFIs. Therapy with radiolabelled tracers is also a potential future application that holds promise for the management of IFIs, particularly for resistant fungi.

References

1.Ankrah AO, Sathekge MM, Dierckx RA, Glaudemans AW. Imaging fungal infections in children. Clin Transl Imaging. 2016;4:57–72. doi: 10.1007/s40336-015-0159-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Ankrah AO, Klein HC, Span LF, de Vries EF, Dierckx RA, Sathekge MM, et al. The role of PET in monitoring therapy in fungal infections. Curr Pharm Des. 2018;24:795–805. doi: 10.2174/1381612824666171213101648. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Update on HIV: Prevention, Treatment and Cure

James cmahon ^1,²

Globally, over 36 million people are infected with HIV with 1 million new infections and nearly 2 million deaths annually. Modern antiretroviral therapy (ART) has transformed the epidemic reducing morbidity and mortality for people with HIV and has now become the cornerstone of preventing onward HIV transmission. This presentation will review the latest updates in the use of ART and other interventions for the treatment of HIV and prevention of HIV transmission.

Despite these advances only one individual has been cured of HIV, but significant progress has been made in understanding the HIV reservoir and measuring the amount of HIV present on ART. This has led to a growing number of clinical trials with interventions aimed at reducing viral persistence in participants on ART and ultimately to allow safe cessation of ART. The presentation will also review the main barriers to HIV cure, methods to measure HIV persistence and clinical strategies that are under evaluation to cure HIV.

Disclosure of interest: J. Mcmahon Conflict with: Institution receives grant funding for research from Viiv, Gilead and Merck.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

White Blood Cell Labeling: Pearls and Pitfalls

Kutlan Ozker ¹

Blood cell radiolabeling (BCR) is a pharmaceutical compounding procedure commonly performed in health care settings such as nuclear medicine laboratories or centralized radiopharmacies which serve multiple institutions. These procedures vary between countries and between health care settings in the same country and even in the same community.

International Society of Radiolabeled Blood Elements (ISORBE) has been trying to help reaching a standard in BCR regarding its safety and usefulness. An important component for reaching a standard in BCR is training the staff in health care settings who are responsible for these procedures.

ISORBE has initiated training programs leading to a certificate of competency starting from 2009. These programs consisting didactic courses and on the job training in the radiolabeling of blood cells have been carried out in several countries. On the other hand there is a global interest in reducing the risks to the patients resulting from pharmaceutical compounding procedures in health care settings. Accordingly, guidelines and regulations were recently implemented to provide safer environments to compound sterile preparations and reduce the consequences of microbial contamination.

This talk will summarize the current guidelines and revisions to United States Pharmacopeia (USP 797) regulations in relation to BCR as a model guideline. Requirements for a model laboratory set up and procedures as well as a training program will be discussed.

References

1.Hung JC. Hepatitis C virus infections from contaminated 99mTc-sestamibi. J Nucl Med. 2007;48:847–8. doi: 10.2967/jnumed.107.040485. [DOI] [PubMed] [Google Scholar]
2.USP-NF General Chapter <797>Pharmaceutical Compounding-Sterile Preparations. USDP 35/NF 30. 2012 [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Molecular Imaging of Infection in the Prosthetic Joint

Christopher J Palestro ¹

Nearly one million lower extremity arthroplasties are performed annually in the United States Aseptic loosening, the most common cause of prosthetic failure, usually is caused by an inflammatory reaction to one or more of the prosthetic components and is managed by a single stage exchange arthroplasty completed in a single hospital admission with one surgical intervention. Infection accounts for about 2% of primary implant failures and about 5% of revision implant failures. Treatment usually involves an excisional arthroplasty followed by antimicrobial therapy and eventually a revision arthroplasty. Because their management is so very different, distinguishing aseptic loosening from infection of a prosthetic joint is extremely important. Joint aspiration with culture is the definitive preoperative diagnostic procedure. Though specific, sensitivity is variable.

The most widely and often the initial radionuclide test performed is bone scintigraphy. Though sensitive it is not specific and is most useful for screening purposes. The accuracy of bone scintigraphy is between 50%>70%. Gallium-67 imaging, which has been used to improve the specificity of bone scintigraphy, has accuracy between 60% and 80%, offers only modest improvement over bone scintigraphy alone and has fallen into disuse.

Currently, the best available imaging test for diagnosing prosthetic joint infection is labeled leukocyte bone marrow imaging with an accuracy of about 90%. All of the studies published over the past three decades confirm that this test is highly specific for infection. In nearly all of the investigations the test has proved to be sensitive as well. Radiolabeled antigranulocyte antibodies and antibody fragments, which are not widely available, have proven to be less accurate than labeled leukocyte/marrow imaging.

In prosthetic joint infection SPECT/CT provides additional important information by precisely localizing abnormalities, and facilitating the differentiation of soft-tissue from bone infection. SPECT/CT potentially could identify other causes of prosthetic failure and the diagnosis could be made more expeditiously.

Diagnosing prosthetic joint infection with FDG-PET has been investigated extensively. After more than 15 years of inconsistent and contradictory results, this test is not a suitable replacement for or alternative to labeled leukocyte/marrow imaging.

The development of an infection specific imaging agent would be a significant improvement. ^99mTc-UBI 29-41, a radiolabeled synthetic fragment of the naturally occurring human antimicrobial peptide ubiquicidin has shown some promise in this regard, but more data are needed.

Reference

1.Palestro CJ. Radionuclide imaging of musculoskeletal infection: A review. J Nucl Med. 2016;57:1406–12. doi: 10.2967/jnumed.115.157297. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging Tuberculosis

Mike Sathekge ¹

Despite extensive research into tuberculosis (TB), significant challenges still exist in its diagnosis, treatment and therapy response assessment. Further the intersection and syndemic interaction between the human immunodeficiency virus (HIV) and TB epidemics continues to have global prevalence with devastating morbidity and massive mortality. Hence the need to review the added value of molecular imaging as a reliable tool in this clinical setting.

The presentation will review and discuss the currently available molecular imaging studies performed to improve our understanding of the pathogenesis of TB infection and assess the value of imaging in the clinical decision making of patients with TB.

Rapidly growing data suggest molecular imaging may add value in:

Detection and assessment of lesion activity and characterizing TB granuloma;
Distinguishing active from inactive disease;
Identification of patterns of metabolic uptake in the lung parenchyma and thoracic nodes;
Prediction of developing active TB from LTBI;
Identification of the risk of developing active TB in patients with old healed TB lesions;
Assessing patients after a clinical cure of pulmonary TB; and
Monitoring response to TB chemotherapy

This talk will have demonstrated that molecular imaging techniques currently available for clinical use in TB imaging shows promising results with the potential for clinical applications in the diagnosis and treatment of TB in clinical practice.

References

1.Lawal I, Zeevaart J, Ebenhan T, Ankrah A, Vorster M, Kruger HG, et al. Metabolic imaging of infection. J Nucl Med. 2017;58:1727–32. doi: 10.2967/jnumed.117.191635. [DOI] [PubMed] [Google Scholar]
2.Ankrah AO, van der Werf TS, de Vries EF, Dierckx RA, Sathekge MM, Glaudemans AW, et al. PET/CT imaging of Mycobacterium tuberculosis infection. Clin Transl Imaging. 2016;4:131–44. doi: 10.1007/s40336-016-0164-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Vorster M, Sathekge MM, Bomanji J. Advances in imaging of tuberculosis: The role of 18F-FDG PET and PET/CT. Curr Opin Pulm Med. 2014;20:287–93. doi: 10.1097/MCP.0000000000000043. [DOI] [PubMed] [Google Scholar]
4.Sathekge M, Maes A, Van de Wiele C. FDG-PET imaging in HIV infection and tuberculosis. Semin Nucl Med. 2013;43:349–66. doi: 10.1053/j.semnuclmed.2013.04.008. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging of Atherosclerosis

Helmut Sinzinger ¹

Molecular imaging of atherosclerosis by positron emission tomography is a great promise for the detection of the activity of underlying biochemical processes and in particular to identify high risk lesions prone to rupture. In time F-18-FDG and F-18-NaF so far are the most widely used compounds. Besides the information on the correlation of uptake with risk factors, risk charts, systemic markers of inflammation, individual clinical prospective value for one particular patient is still doubtful.

We examined the F-18-FDG and F-18-NaF uptake in experimental atherosclerotic lesions (after abrasion with a Fogarthy catheter) in normo- and hypercholesterolemic New Zealand white rabbits. Furthermore, atherosclerotic lesions as well as cultured endothelial and smooth muscle cells, monocytes/macrophages were investigated ex-vivo and in-vitro.

In-vitro as well as ex-vivo findings from excised lesions indicate, that the F-18-FDG uptake in SMC depends on the metabolic activity. Activated SMC uptake may exceed by far (max. + 47%) the one of monocyte-derived macrophages. Although foam cells have been claimed to be the key target of F-18-FDG, studies on isolated cells demonstrated that per cell the uptake is the highest in endothelial cells and in activated smooth muscle cells, which contribute to the stabilization of the lesion rather than the progression of the disease. On the other hand, depending on the lesion stages, the relative content of the different cell types varies considerably. Different types of calcification as well as inflammation are processes taking place at the same time in one particular lesion site. Microcalcifications are known to promote plaque rupture, these findings on a cellular level are also significantly influenced by the drug intake, particularly the one of statins.

Various pathobiochemical mechanisms going on in an arterial lesion at the same time with a different uptake behaviour make an identification of a special lesion type by molecular imaging very difficult. The ubiquitous presence of F-18-FDG in contrast to F-18-NaF makes it unlikely that it may become in the future a promising marker for the early identification of unstable human atherosclerotic lesions prone to rupture.

References

1.Brammen L, Palumbo B, Lupattelli G, Sinzinger H. Is (18)F-FDG PET really a promising marker for clinically relevant atherosclerosis? Hell J Nucl Med. 2014;17:62–3. [PubMed] [Google Scholar]
2.Brammen L, Steiner S, Berent R, Sinzinger H. Molecular imaging of atherosclerotic lesions by positron emission tomography –Can it meet the expectations? Vasa. 2016;45:125–32. doi: 10.1024/0301-1526/a000506. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Which, Where and When to Select Radioantibiotics, Labelled Leucocytes and Radiolabelled Peptides for Infection/Inflammation

Victoria Soroa ¹

Revision of the principles for radiolabelling leucocytes, antibiotics, peptides & ¹⁸F-FDG in pursuit of the infection/inflammation diagnostic functional image for infection/inflammation. Short description of mentioned methodologies: labeled leucocytes-Tc99m, ciprofloxacin-Tc99m, ceftizoxim-Tc99m, ubiquicidin-Tc99m and FDG-F18 will be given. New instrumentation, hybrid images and software should influence the selection and available possibilities in the working place.

Application of the radiolabelled agents will depend on clinical presentation, site, and time of the event, technical expertise & availability in the region.

Correct application of the different methods discussed, depending on the patient´s presentation and urgency of diagnostic response. Consider controversies and pitfalls of the expected images With the scenario of traditional and new radiolabelled agents the attendees will be capable of applying the most suitable appropriate radiomolecule for the infection/inflammation diagnosis and follow-up of the patient´s pathology.

References

1.Jamar F, Buscombe J, Chiti A, Christian PE, Delbeke D, Donohoe KJ, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54:647–58. doi: 10.2967/jnumed.112.112524. [DOI] [PubMed] [Google Scholar]
2.Erba PA, Conti U, Lazzeri E, Sollini M, Doria R, De Tommasi SM, et al. Added value of 99mTc-HMPAO-labeled leukocyte SPECT/CT in the characterization and management of patients with infectious endocarditis. J Nucl Med. 2012;53:1235–43. doi: 10.2967/jnumed.111.099424. [DOI] [PubMed] [Google Scholar]
3.Lupetti A, Nibbering PH, Welling MM, Pauwels EK. Radiopharmaceuticals: New antimicrobial agents. Trends Biotechnol. 2003;21:70–3. doi: 10.1016/s0167-7799(02)00032-x. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Tracking Virus Infection and Immune Responses In Vivo: From Macro to Microscopic Characterization

Francois Villinger ¹

While the interplay of host and pathogens has been followed in detail using rodent models and fluorescent based technologies, larger animal models and humans present challenges for technologies that do not penetrate deep into tissues.

We have therefore developed and optimized a method to image pathogens and immune markers in nonhuman primates using a combination of isotope and fluorescent labeled ligands to map host pathogen interactions in real time using a combination of immunoPET/CT followed by targeted sampling of tissues of interest and analysis of such tissue at the cellular and subcellular level using confocal microscopy and flow cytometry.

In the context of simian immunodeficiency virus (SIV) infection of rhesus macaques as a model of human HIV infection, we have been able to interrogate virus and CD4 T cell dynamic during acute and chronic infection, upon antiretroviral therapy (ART) initiation, identifying sanctuaries of continued low levels of replicating virus as well as identifying functional virus reservoir from which virus rebounds upon ART interruption. Data obtained from these analyses show early saturation of upper lymphoid tissues before a massive shift to gastrointestinal tissues (GI) upon SIV infection, with the GI harboring viral sanctuaries and functional viral reservoirs. However, this technology can also serve to identify the dynamics of immunogens following immunization identifying immune draining sites, advancing our understanding of immune mechanisms of elaboration of immune responses and the identification of potential limitations.

Moreover, unlike techniques that use recombinant pathogens expressing a reporter, many of the techniques developed may readily translate the clinic, providing novel investigative tools with which to monitor therapeutic progress and clinical trials.

Disclosure of interest: F Villinger - Conflict with NIH grant.

References

1.Santangelo PJ, Rogers KA, Zurla C, Blanchard EL, Gumber S, Strait K, et al. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods. 2015;12:427–32. doi: 10.1038/nmeth.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, et al. Sustained virologic control in SIV+macaques after antiretroviral and a4b7 antibody therapy. Science. 2016;354:197–202. doi: 10.1126/science.aag1276. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging Vascular Graft Infection

Mariza Vorster ¹

The infection rates of vascular grafts are low. However, when infection occurs, it tends to be associated with high rates of morbidity and mortality. Timely non-invasive and reliable detection with SPECT or PET imaging may play an important role in the management of these patients.[1] The objectives are:

Identification of both SPECT and PET tracers used in vascular graft imaging and understanding the various advantages and limitations of these;
Pattern recognition in the interpretation of infected vs non-infected vascular grafts;
Understanding the role of Nuclear Medicine in the imaging of infected vascular grafts

An overview of the most relevant/robust publications and sharing of experience from our center.

SPECT imaging options include labeled leukocytes and Ga-67 citrate, whereas ¹⁸F-FDG PET/CT imaging is best validated.[1]

Review of a large cohort of patients with different types of vascular grafts concluded that the majority of non-infected vascular grafts demonstrated a diffuse pattern of FDG uptake, which remained unchanged over time.[2] Imaging with ¹⁸F-FDG PET/CT in patients with suspected vascular graft infection demonstrates high accuracy and could play an important role in the early detection and monitoring of treatment response in such patients.[3]

Imaging with ¹⁸F-FDG PET/CT appears to be a valuable tool which demonstrates high accuracy in patients with suspected vascular graft infection. Knowledge of the various patters and potential pitfalls that may be encountered in different clinical settings may avoid misinterpretation and optimize patient management.

References

1.Nagpal A, Sohail MR. Prosthetic vascular graft infections: A contemporary approach to diagnosis and management. Curr Infect Dis Rep. 2011;13:317–23. doi: 10.1007/s11908-011-0191-y. [DOI] [PubMed] [Google Scholar]
2.Keidar Z, Pirmisashvili N, Leiderman M, Nitecki S, Israel O. 18F-FDG uptake in noninfected prosthetic vascular grafts: Incidence, patterns, and changes over time. J Nucl Med. 2014;55:392–5. doi: 10.2967/jnumed.113.128173. [DOI] [PubMed] [Google Scholar]
3.Keidar Z, Nitecki S. FDG-PET in prosthetic graft infections. Semin Nucl Med. 2013;43:396–402. doi: 10.1053/j.semnuclmed.2013.04.004. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Molecular Imaging: Multimodality Imaging

Weibo Cai ¹

Each molecular imaging technique has its strengths and weaknesses. Combining different imaging modalities in a rational manner will provide complementary or synergistic information. In this talk, I will briefly present some background about each molecular imaging technique, and then give some examples about the recent development of multimodality imaging agents.

The learning objectives are:

1)
Understand the basics of various molecular imaging techniques
2)
Understand how to design and prepare multimodality imaging agents
3)
Understand how different imaging techniques can be used to provide complementary and/or synergistic information

Reference

1.Rieffel J, Chitgupi U, Lovell JF. Recent advances in higher-order, multimodal, biomedical imaging agents. Small. 2015;11:4445–61. doi: 10.1002/smll.201500735. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

When Particles Meet…. Interaction of Radiation with Nanoparticles

Jan Grimm ¹

Nanotechnology has been used in cancer therapy and diagnosis for quite some time. Nanoparticles possess several desirable features for use in imaging and therapy. They serve as platforms for loading therapeutics and contrast agents while simultaneously anchoring targeting ligands or stealth polymer coatings. Their size and surface chemistry can be tuned such that they exhibit attractive biological properties, such as passive accumulation and retention in cancer, in contrast to the rapid washout often observed by small molecular imaging agents. Among the many imaging modalities that have adopted nanoparticle-based contrast agents are nuclear imaging techniques such as PET or SPECT. Consequently, radiolabeled nanoparticles are of great interest to the nuclear imaging and nano-oncology communities.

Radiolabeling of nanoparticles has been achieved via surface functionalization of chelating agents that bind specific radioisotopes. This approach enables utilization of labeling protocols that have already been established in molecular chelator research but presents several well-known disadvantages since there is no molecular chelator that fits to all radioisotopes, there is no one-stop-shop approach. To solve this issue, we have devised a method that allows for exactly that – a chelator-free radiolabeling method that allows to create inherently radioactive particles for diagnosis and therapy. This combination of radiotracers with nanoparticles also allows for some new imaging modalities due to the interaction of the payload with the particles, which will be shown in more depth. Using Cerenkov light from the radiotracer, we used nanoparticles and fluorochromes to shift the light from blue to greater penetrating red light and have created switchable nanoagents based on radioactivity.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Probe Development – Small Molecule Agents in Neuroscience

Michael Kassiou ¹

The development of small molecule probes for use in neurosceince provides a unique opportunity to study human health. It aids in diagnosis and understanding of neurodegenerative diseases, assists with streamlining of drug development and in the validation of animal models of disease. The latest developments in the field will be discussed.

Reference

1.Vāvere AL, Scott PJ. Clinical applications of small-molecule PET radiotracers: Current progress and future outlook. Semin Nucl Med. 2017;47:429–53. doi: 10.1053/j.semnuclmed.2017.05.001. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Molecular Imaging Probe Development – Nanoparticles

Dong Soo Lee ¹

Radionanomedicine is the combined approach of nuclear medicine and nanomedicine. Radioisotopes such as Tc-99m (SPECT; single photon emission combined tomography) or Cu-64 (PET: positron emission tomography) are used as diagnostic-imaging help to nanomedicine and radioisotopes such as Lu-177 and Y-90 for therapy aide. Radionanomedicine can be divided to exogenous or endogenous ones.

Exogenous radionanomedicine uses mostly inorganic materials such as iron oxide, gold, silica and doped nanoparticles (upconversion nanoparticle). It also can use organic materials of micelle or liposomes. We can use trace amount (nanomole) and avoid concerns of safety and also use tracer kinetic to elucidate the biodistribution with imaging and quantification. Using Ga-68-DOTA-labeled iron oxide, fluorescent-labeled SERS (surface enhanced Raman scattering) dots, and Cu-64 labeled UCNP (upconversion nanoparticles), we could 1) characterize sentinel lymph nodes using mannose-macrophage targeting, 2) FRES (fluorescence-Raman endoscopic system) imaging of HER2/EGFR1 receptors or VEGF on the surface of the tumours and 3) rapid hepatobiliary excretion of 40 nm-sized encapsulated UCNPs, respectively.

Endogenous radionanomedicine recently adopted endogenous organic nanovesicles which are collectively called extracellular vesicles (EVs) consisting of exosomes and microvesicles. Liposomes are void surrogate (of EVs) artificially made to mimic exosomes. EVs were proposed to replace cell therapy. Instead of fluorescent dyes, Tc-99m HMPAO or Cu-64 DOTA could label EVs to reveal biodistribution on SPECT or PET. Migration of EVs on microfluidic chips and their functional activity using luciferase-reporter or graphene-oxide-reporter could simulate intercellular in vivo action of EVs successfully in vitro. Thus, understanding of whereabouts and action at target sites (cells) of EVs were recently enabled by endogenous radionanomedicine and molecular imaging on a chip.

In vivo application needs further progress in understanding innate immune responses to these radiolabeled nanomaterials. Differential uptake by Kupffer cells and hepatocytes are to be interpreted on their characteristic molecular mechanism to naked, corona-protein labeled or PEGylated nanomaterials. Radiolabeled nanomaterials will soon elucidate the exact biodistribution affected by physiology and bodily immune responses to nanomaterials.

Reference

1.Lee DS, editor. Radionanomedicine: Combined Nuclear and Nanomedicine. Springer; 2018. [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Measuring the Dopamine Response to Cigarette Smoking in Men and Women with “lpntPET”: Tuning the Kinetic Model to Capture Dopamine Fluctuations

Evan Morris ¹

PET imaging with neuroreceptor tracers has been used successfully to monitor changes in a neurotransmitter which competes with a given tracer at a specific binding site. Assays of stimulus-induced dopamine release have become a standard use of PET for studying addiction and other psychiatric disorders. Sometimes, as with cigarette smoking, the dopamine response is short-lived and conventional kinetic models are not well-suited to detect changes in the PET signal caused by these brief events. In such cases, conventional approaches to analysis with time-invariant kinetic parameters can lead to highly variable or conflicting findings. (Simulation Study). Realistic noisy phantom images of dynamic PET data containing known responses to dopaminergic stimuli were created. Design parameters such as activity dose, mode of tracer administration (bolus vs bolus/infusion), duration of study and timing of stimulus were examined to determine the optimal PET experiment for detecting and characterizing the response to smoking. (Experiment with smokers). Eight female and 8 male smokers were scanned after overnight abstinence with ¹¹C-raclopride PET. Each subject smoked one of his or her own cigarettes while in the PET scanner. lpntPET was applied at the voxel level to create spatio-temporal patterns of dopamine release in the striatum for each participant.

Simulations. For a study with ¹¹C-raclopride with smoking at 35 minutes into the scan, 75 minutes of scanning following a bolus injection was deemed optimal for detection of the dopamine response. Experiment. Male smokers were found to have significant dopamine release in the right ventral striatum during smoking but female smokers did not. Preliminarily, we have also identified a locus in the dorsal striatum where female smokers respond faster than males to smoking.

The optimization of the experiment has allowed us to shorten the scan time and simplify the experimental protocol without sacrificing sensitivity. The finding of sex-differences in the ventral striatal dopaminergic response to smoking a cigarette may be an important aspect of the known behavioural differences in smoking and in response to medications for smoking.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Molecular Imaging Probe Development-Reporter Genes

Hyewon Youn ¹

In molecular biology, many reporter genes have been developed for monitoring cellular processes. Development of controlled gene delivery system promotes to construct various types of reporter genes for monitoring the level of a gene expression, the promoter activity, or protein-protein interaction. By placing an imaging reporter gene under the control of a promoter, the amount of reporter protein can be dynamically visualized in vivo. In addition, various instrumental advances in molecular imaging have been facilitating the sensitivity and resolution of in vivo reporter imaging. Here, I will summarize the basic concept and the strategies of reporter imaging. I will also introduce various reporter genes which are frequently used in optical, nuclear medicine, and magnetic resonance imaging for in vivo application. Each modality has its unique advantages and disadvantages, and therefore, appropriate choices should be made by each specific situation. For better understanding of reporter imaging, I will explain typical examples of reporter gene imaging. Though several types of reporters and multimodal imaging instruments are currently available, more efficient multimodal reporter gene system and detectors compatible with several imaging modalities are still required, and I will also summarize recent advances in multimodal reporters.

Reference

1.Youn H, Chung JK. Reporter gene imaging. AJR Am J Roentgenol. 2013;201:W206–14. doi: 10.2214/AJR.13.10555. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Musculoskeletal: Bone Scanning in Relation to Hip Prostheses

Stephen Allwright ¹

The aim is to understand the variety of patterns associated with complications related to hip prostheses and their biomechanical aetiologies. We will review case studies demonstrating a variety of complications and a discussion of the points to look for to try and distinguish the various aetiologies and their relationship to patient symptoms. The desired outcome is to recognise various common patterns around hip prostheses and to have a biomechanical approach to assessing possible aetiologies in uncommon patterns.

Reference

1.Cooper R, Allwright S, Anderson J. Atlas of Nuclear Imaging in Sports Medicine. McGraw-Hill; 2003. [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Update on Radiosynovectomy for Hemophilic Arthropathy and Rheumatoid Arthritis

Emerita Barrenechea ¹

Radiosynovectomy (RS) is the radionuclide therapy of joint synovitis by intraarticular injection of Yttrium-90. Terbium-169 or Rhenium-186 and newer radionuclides. The mechanism of this procedure is that the radioactive particles are absorbed by the superficial cells of the synovium and the beta radiation leads to coagulation necrosis and sloughing of these cells. Despite its efficacy, it is underutilized. It is therefore the aim of this presentation to prove it is highly effective in hemophilic arthropathy (HA) and rheumatoid arthiritis (RA). Documented cases of hemophilia and rheumatoid arthritis will be included. They will be treated with Yttrium silicate for larger joints (knees) and Rhenium 186 for medium sized joints. There has been an overall success in RS among hemophiliacs of 86% and 70% in RA based on baseline parameters and at the end of the study. A meta-analysis of other publications will be cited. Radisynovectomy is a safe and cost-effective treatment for hemophilic arthropathy and rheumatoid arthritis. Other benefits include that this procedure can be done on an outpatient basis, and no rehabilitation needed, lower Factor 8 replacement for coagulopathy in hemophiliacs compared to 100% when they undergo surgery. There has been no reports of secondary malignancy in long term studies.

References

1.Rodriguez-Merchan EC, De La Corte-Rodriguez H. Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different? Thromb Res. 2016;140:41–5. doi: 10.1016/j.thromres.2016.02.007. [DOI] [PubMed] [Google Scholar]
2.Long Term Results of 500 Cases in 38 Years Study: World Hemophilia Foundation Guidelines. 2015 [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Single Photon Emission Computed Tomography/Computed Tomography in Indeterminate Bone Lesions

Sai Han ¹

Nuclear Medicine plays an important role in the investigations of benign and malignant bone diseases. Planar and SPECT bone scintigraphy have limited anatomical and structural information and frequently gives inconclusive results with a potential diagnostic delay. The addition of CT to nuclear medicine provides functional activity plus better localisation and characterisation of the lesions. SPECT/CT has been shown to be superior to both Planar and SPECT imaging in solving indeterminate bone lesions. Similarly, equivocal bone lesions on XR, CT and MRI can be correlated with nuclear medicine to assess their activity. SPECT/CT bone assessment requires both nuclear medicine and musculoskeletal CT skills, and a structured reporting approach is useful in our practice. The standard reporting should start with reviewing Planar images aided by relevant clinical information and previous imaging findings. If the scans need further clarification, patients can proceed with SPECT/CT in the same session. Better localisation will clarify the origin whether artefacts, soft tissue pathology or skeletal lesions. Better morphological assessment on CT can identify whether sclerotic, lytic or mixed lesions, and aggressive or nonaggressive lesions etc. Anatomy and morphology-based interpretation helps reach a conclusive diagnosis in a timely manner and also can detect critical findings such as risk of pathological fractures, potential threat to spinal canal etc. Hybrid imaging can also uncover significant incidental pathologies such as soft tissue mass, lymphadenopathy etc. This talk will go through the strengths and limitations of SPECT/CT reporting with example cases including traumatic, metabolic, inflammatory, degenerative and neoplastic bone lesions.

References

1.Sharma P, Kumar R, Singh H, Bal C, Julka PK, Thulkar S, et al. Indeterminate lesions on planar bone scintigraphy in lung cancer patients: SPECT, CT or SPECT-CT? Skeletal Radiol. 2012;41:843–50. doi: 10.1007/s00256-011-1304-2. [DOI] [PubMed] [Google Scholar]
2.Mahaletchumy T, AbAziz A. Incremental value of single-photon emission computed tomography-computed tomography for characterization of skeletal lesions in breast cancer patients. World J Nucl Med. 2017;16:303–10. doi: 10.4103/1450-1147.215496. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Single Photon Emission Computed Tomography/Computed Tomography in Charcot Osteoarthropathy-Lessons from a Multidisciplinary Diabetic Foot Service

Nicola Mulholland ¹

Charcot neuropathic osteoarthropathy (CN) is a bone and joint complication of diabetes which poses significant challenge in clinical practice. Trauma to the neuropathic foot leads to an inflammatory and osteoclastic response, which can lead to fracture, bone fragmentation and joint destruction. This evolves into severe foot deformity i.e. the Charcot foot. Charcot foot is a major cause of morbidity and debilitation for people living with diabetes, and prompt management is indicated to prevent complications. Drawing on illustrated case examples and algorithms from Kings diabetic foot unit, an internationally recognized centre of excellence with low amputation rate and one of the largest and oldest in UK, this talk will discuss our clinical and imaging approach to management of acute Charcot Foot, particularly with reference to imaging. Learning objectives are:

To understand the pathophysiology of Charcot foot
To be able to recognise the clinical presentation and understand limitations of pre-imaging investigations
To understand the role of SPECT CT in the management of Charcot osteoarthropathy.

References

1.Petrova NL, Edmonds ME. Acute charcot neuro-osteoarthropathy. Diabetes Metab Res Rev. 2016;32(Suppl 1):281–6. doi: 10.1002/dmrr.2734. [DOI] [PubMed] [Google Scholar]
2.Manu CA, Mustafa OG, Bates M, Vivian G, Mulholland N, Elias D, et al. Transformation of the multidisciplinary diabetic foot clinic into a multidisciplinary diabetic foot day unit: Results from a service evaluation. Int J Low Extrem Wounds. 2014;13:173–9. doi: 10.1177/1534734614545877. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Role of Positron Emission Tomography in Vasculitis and Polymyalgia Rheumatica

Claire E Owen ¹

Giant cell arteritis (GCA) is a large vessel vasculitis affecting the aorta and its branches. Whilst cranial cases are more easily diagnosed, 10% of patients exhibit only constitutional symptoms and raised inflammatory markers, with a further 15% presenting as pyrexia of unknown origin.[1,2] At diagnosis, extra-cranial involvement is seen in 45% and importantly can lead to complications including aneurysm formation and dissection.[3,4] Whilst temporal artery biopsy remains the gold standard, PET can prevent missed diagnosis, document the extent of extra-cranial involvement and provide long-term prognostic information. Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder characterised by subacute onset shoulder and pelvic girdle pain, and early morning stiffness. Diagnosis is based upon a clinical construct and raised inflammatory markers, with concomitant GCA recognised in 16-21% of cases.[5] Initial studies focussed on the incidence of subclinical large vessel vasculitis in PMR, however the ability of PET to detect articular inflammation has more recently led to recognition of a distinctive pattern of abnormal ¹⁸F-FDG uptake at the shoulders, hips, interspinous bursae and adjacent to the ischial tuberosities in this condition.

The aims are to:

1)
understand the role of PET in the diagnosis and management of large vessel vasculitis
2)
Appreciate how PET has contributed to our understanding of the pathology of polymyalgia rheumatica
3)
Learn the imaging phenotype of polymyalgia rheumatica on PET and understand the potential clinical applications of this imaging modality in this condition.

References

1.Gonzalez-Gay MA, Barros S, Lopez-Diaz MJ, Garcia-Porrua C, Sanchez-Andrade A, Llorca J, et al. Giant cell arteritis: Disease patterns of clinical presentation in a series of 240 patients. Medicine (Baltimore) 2005;84:269–76. doi: 10.1097/01.md.0000180042.42156.d1. [DOI] [PubMed] [Google Scholar]
2.Calamia KT, Hunder GG. Giant cell arteritis (temporal arteritis) presenting as fever of undetermined origin. Arthritis Rheum. 1981;24:1414–8. doi: 10.1002/art.1780241113. [DOI] [PubMed] [Google Scholar]
3.Schmidt WA, Seifert A, Gromnica-Ihle E, Krause A, Natusch A. Ultrasound of proximal upper extremity arteries to increase the diagnostic yield in large-vessel giant cell arteritis. Rheumatology (Oxford) 2008;47:96–101. doi: 10.1093/rheumatology/kem322. [DOI] [PubMed] [Google Scholar]
4.Nuenninghoff DM, Hunder GG, Christianson TJ, McClelland RL, Matteson EL. Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: A population-based study over 50 years. Arthritis Rheum. 2003;48:3522–31. doi: 10.1002/art.11353. [DOI] [PubMed] [Google Scholar]
5.Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008;372:234–45. doi: 10.1016/S0140-6736(08)61077-6. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Single Photon Emission Computed Tomography/Computed Tomography in the Painful Knee Replacement

Arum Parthipun ¹

The aim of this presentation is to familiarise anyone reporting bone scintigraphy with the basic principles of interpreting SPECT/CT of knee replacements. We will cover some of the technical challenges in acquiring high quality images, including configuration of the CT component of the SPECT/CT. We will learn how to assess component positioning using CT, and how this knowledge will aid interpretation of the bone SPECT findings. Finally, we will review some common complications of knee replacements.

References

1.Chauhan SK, Clark GW, Lloyd S, Scott RG, Breidahl W, Sikorski JM, et al. Computer-assisted total knee replacement. A controlled cadaver study using a multi-parameter quantitative CT assessment of alignment (the perth CT protocol) J Bone Joint Surg Br. 2004;86:818–23. doi: 10.1302/0301-620x.86b6.15456. [DOI] [PubMed] [Google Scholar]
2.Berger RA, Rubash HE, Seel MJ, Thompson WH, Crossett LS. Determining the rotational alignment of the femoral component in total knee arthroplasty using the epicondylar axis. Clin Orthop Relat Res. 1993;286:40–7. [PubMed] [Google Scholar]
3.Berger RA, Crossett LS, Jacobs JJ, Rubash HE. Malrotation causing patellofemoral complications after total knee arthroplasty. Clin Orthop Relat Res. 1998;356:144–53. doi: 10.1097/00003086-199811000-00021. [DOI] [PubMed] [Google Scholar]
4.Smith SL, Wastie ML, Forster I. Radionuclide bone scintigraphy in the detection of significant complications after total knee joint replacement. Clin Radiol. 2001;56:221–4. doi: 10.1053/crad.2000.0620. [DOI] [PubMed] [Google Scholar]
5.Hirschmann MT, Konala P, Iranpour F, Kerner A, Rasch H, Friederich NF, et al. Clinical value of SPECT/CT for evaluation of patients with painful knees after total knee arthroplasty –a new dimension of diagnostics? BMC Musculoskelet Disord. 2011;12:36. doi: 10.1186/1471-2474-12-36. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Hirschmann MT, Iranpour F, Konala P, Kerner A, Rasch H, Cobb JP, et al. A novel standardized algorithm for evaluating patients with painful total knee arthroplasty using combined single photon emission tomography and conventional computerized tomography. Knee Surg Sports Traumatol Arthrosc. 2010;18:939–44. doi: 10.1007/s00167-010-1070-z. [DOI] [PubMed] [Google Scholar]
7.Al-Nabhani K, Michopoulou S, Allie R, Alkalbani J, Saad Z, Sajjan R, et al. Painful knee prosthesis: Can we help with bone SPECT/CT? Nucl Med Commun. 2014;35:182–8. doi: 10.1097/MNM.0000000000000028. [DOI] [PubMed] [Google Scholar]
8.Hirschmann MT, Amsler F, Rasch H. Clinical value of SPECT/CT in the painful total knee arthroplasty (TKA): A prospective study in a consecutive series of 100 TKA. Eur J Nucl Med Mol Imaging. 2015;42:1869–82. doi: 10.1007/s00259-015-3095-5. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Single Photon Emission Computed Tomography/Computed Tomography in Foot/Ankle Pain

Arum Parthipun ¹

The aim of this presentation is to demonstrate how SPECT/CT is invaluable in evaluating patients with pain in the foot or ankle. We will begin with describing how to acquire the best quality images, including CT reconstruction techniques. We will review the relevant anatomy of the foot and ankle, and then we will look at the evidence for SPECT/CT for specific indications and how your reports can be used to assist patient management.

References

1.Chicklore S, Gnanasegaran G, Vijayanathan S, Fogelman I. Potential role of multislice SPECT/CT in impingement syndrome and soft-tissue pathology of the ankle and foot. Nucl Med Commun. 2013;34:130–9. doi: 10.1097/MNM.0b013e32835c0964. [DOI] [PubMed] [Google Scholar]
2.Ha S, Hong SH, Paeng JC, Lee DY, Cheon GJ, Arya A, et al. Comparison of SPECT/CT and MRI in diagnosing symptomatic lesions in ankle and foot pain patients: Diagnostic performance and relation to lesion type. PLoS One. 2015;10:e0117583. doi: 10.1371/journal.pone.0117583. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Hassink G, Testa EA, Leumann A, Hügle T, Rasch H, Hirschmann MT, et al. Intra- and inter-observer reliability of a new standardized diagnostic method using SPECT/CT in patients with osteochondral lesions of the ankle joint. BMC Med Imaging. 2016;16:67. doi: 10.1186/s12880-016-0169-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Knupp M, Pagenstert GI, Barg A, Bolliger L, Easley ME, Hintermann B, et al. SPECT-CT compared with conventional imaging modalities for the assessment of the varus and valgus malaligned hindfoot. J Orthop Res. 2009;27:1461–6. doi: 10.1002/jor.20922. [DOI] [PubMed] [Google Scholar]
5.Mohan HK, Gnanasegaran G, Vijayanathan S, Fogelman I. SPECT/CT in imaging foot and ankle pathology-the demise of other coregistration techniques. Semin Nucl Med. 2010;40:41–51. doi: 10.1053/j.semnuclmed.2009.08.004. [DOI] [PubMed] [Google Scholar]
6.Nathan M, Mohan H, Vijayanathan S, Fogelman I, Gnanasegaran G. The role of 99mTc-diphosphonate bone SPECT/CT in the ankle and foot. Nucl Med Commun. 2012;33:799–807. doi: 10.1097/MNM.0b013e328355880b. [DOI] [PubMed] [Google Scholar]
7.Pagenstert GI, Barg A, Leumann AG, Rasch H, Müller-Brand J, Hintermann B, et al. SPECT-CT imaging in degenerative joint disease of the foot and ankle. J Bone Joint Surg Br. 2009;91:1191–6. doi: 10.1302/0301-620X.91B9.22570. [DOI] [PubMed] [Google Scholar]
8.Parthipun A, Moser J, Mok W, Paramithas A, Hamilton P, Sott AH, et al. 99mTc-HDP SPECT-CT aids localization of joint injections in degenerative joint disease of the foot and ankle. Foot Ankle Int. 2015;36:928–35. doi: 10.1177/1071100715579263. [DOI] [PubMed] [Google Scholar]
9.Singh VK, Javed S, Parthipun A, Sott AH. The diagnostic value of single photon-emission computed tomography bone scans combined with CT (SPECT-CT) in diseases of the foot and ankle. Foot Ankle Surg. 2013;19:80–3. doi: 10.1016/j.fas.2012.11.002. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Interesting Cases in Musculoskeletal Single Photon Emission Computed Tomography/Computed Tomography

Qaisar Siraj ¹

Bone SPECT and/or SPECT/CT is the second most frequently performed SPECT examination in routine nuclear medicine. Planar bone scintigraphy may not give enough information for lesion detection or anatomic localization in the evaluation of large and complex bony structures like base of skull, spine, pelvis and hips as well as small bones and joint regions. Hybrid SPECT-CT however allows detection of subtle, nonspecific abnormalities on bone scans and interprets them as specific focal areas of pathology. Both bone and soft-tissue lesions can both be visualized and identified with a high degree of accuracy. The SPECT component of the SPEC/CT increases image contrast and improves lesion detection and localization whereas the CT component of SPECT/CT provides incremental and complementary diagnostic information improving specificity and accuracy of diagnosis but also provides additional diagnoses. Musculoskeletal SPECT/CT provides documented unique diagnostic information in cases of femoral head AVN, in defining the cause of back pain, for differentiating between malignant and benign spinal lesions, in subtle bone trauma, in bone infection, etc. Multimodality fusion imaging increases the specificity of the physiologic modality as well as increasing the sensitivity of the anatomic modality. A number of interesting cases are presented which provide suitable examples of the unique diagnostic role of musculoskeletal SPECT/CT.

References

1.Van der Wall H, Lee A, Magee M, Frater C, Wijesinghe H, Kannangara S, et al. Radionuclide bone scintigraphy in sports injuries. Semin Nucl Med. 2010;40:16–30. doi: 10.1053/j.semnuclmed.2009.08.006. [DOI] [PubMed] [Google Scholar]
2.Scharf S. SPECT/CT imaging in general orthopedic practice. Semin Nucl Med. 2009;39:293–307. doi: 10.1053/j.semnuclmed.2009.06.002. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Changing Role of Nuclear Medicine in Sports Medicine in the Era of Magnetic Resonance Imaging-Where to Next?

Hans Van Der Wall ¹

Nuclear Medicine is in decline as a modality for imaging sporting injuries as MRI becomes increasingly available and the cost declines. We need to find methods of imaging disease that MRI has no capacity to address. Mechanical dysfunction of the sacroiliac joint (SIJ) is such a disease with the bone scan being accurate and reproducible in imaging the primary cause and secondary manifestations. We have imaged over 3000 cases of mechanical dysfunction of the SIJ by bone scintigraphy with SPECT/CT. All patients fulfilled the clinical guidelines for the diagnosis. Patients demonstrated uptake in the dorsal interosseous ligament (DIOL) of the SIJ which could be quantified. Enthesopathy of the adductor, hamstring, psoas and gluteus medius tendons were apparent with a significant proportion also showing hip impingment. SPECT/CT of bone scintigraphy detected the mechanical dysfunction of the SIJ with a sensitivity and specificity of over 95%> Uptake in the damaged DIOL had a value of 1 in the ROI analysis. Treatment with directed physiotherapy improved pain in 80%. Proplotherapy or platelet rich plasma injection into the ligament improved a high proportion of the remainder. SIJ mechanical dysfunction accounts for 23-30% of lateralising lower back pain compared to intervertebral disc injury (15%). Clinical diagnosis is complex and requires a high level of expertise and training. SPECT/CT has firm criteria that enables an accurate and reproducible result.

References

1.Cusi M, Saunders J, Van der Wall H, Fogelman I. Metabolic disturbances identified by SPECT-CT in patients with a clinical diagnosis of sacroiliac joint incompetence. Eur Spine J. 2013;22:1674–82. doi: 10.1007/s00586-013-2725-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Vleeming A, Albert HB, Ostgaard HC, Sturesson B, Stuge B. European guidelines for the diagnosis and treatment of pelvic girdle pain. Eur Spine J. 2008;17:794–819. doi: 10.1007/s00586-008-0602-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Neuroscience: Stroke, Vascular Disease and Dementia

Christopher Chen ¹

Stroke is a leading cause of death and disability worldwide. Despite remarkable improvements in acute stroke treatment, many patients only make a partial or poor recovery, in terms of cognition as well as other neurological deficits. Although a substantial proportion of patients after non-disabling stroke are cognitively impaired compared to aged and education matched community dwelling controls and remain at an increased risk of incident dementia, it is increasingly apparent that covert stroke is an under-recognised but important cause of cognitive impairment and dementia – hence it is an important focus of future research.

This review will emphasise that:

a)
cerebrovascular disease (CeVD) is highly prevalent in elderly people and make important contributions to cognitive impairment and dementia in later life;
b)
MRI can be used to demonstrate CeVD burden by use of established and novel imaging markers;
c)
Many people with dementia have mixed pathology (commonly AD and CeVD) and CeVD can be additive with AD pathology in impairing cognitive function and increasing the likelihood of dementia.

Whilst advances in stroke management, and the recognition of the co-existence of vascular dementia and Alzheimer’s disease have opened new prospects for the prevention and treatment of vascular cognitive impairment (VCI) and dementia, we need to improve our understanding of biomarkers and mechanisms so that successful treatment and prevention trials for VCI can be performed.

References

1.van der Flier WM, Skoog I, Schneider JA, Pantoni L, Mok V, Chen CLH, et al. Vascular cognitive impairment. Nat Rev Dis Primers. 2018;4:18003. doi: 10.1038/nrdp.2018.3. [DOI] [PubMed] [Google Scholar]
2.van Veluw SJ, Shih AY, Smith EE, Chen C, Schneider JA, Wardlaw JM, et al. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 2017;16:730–40. doi: 10.1016/S1474-4422(17)30196-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Skrobot OA, O'Brien J, Black S, Chen C, DeCarli C, Erkinjuntti T, et al. The vascular impairment of cognition classification consensus study. Alzheimers Dement. 2017;13:624–33. doi: 10.1016/j.jalz.2016.10.007. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Magnetic Resonance Imaging in Focal Epilepsy

Greg Fitt ¹

In patients with intractable focal epilepsy, detection of a surgically resectable epileptogenic lesion has a major impact on patient management. Many epileptogenic lesions are subtle and detection requires high quality epilepsy-directed MRI technique, preferably at 3 Tesla. This includes whole brain volumetric T1-weighted scans and whole brain volumetric FLAIR (FLuid Attenuated Inversion Recovery) or DIR (Double Inversion Recovery) scans. From these volumetric acquisitions, images are reformatted in sagittal plane and tilted coronal and axial plane (perpendicular and parallel to the hippocampi respectively). In some patients, oblique or curved reformatted images are obtained to assess gyral anatomy and pathology. Tilted coronal T2 weighted imaging, axial DWI (Diffusion Weighted Imaging), SWI (Susceptibility Weighted Imaging) are routinely performed. In selected patients, advanced MRI techniques can be helpful including fMRI (functional MRI) to localize eloquent brain regions and to assess brain connectivity and occasionally ictal fMRI. Other advanced MRI techniques such as Diffusion Tensor Imaging, to assess white matter tract disruption, and morphometric MRI analysis, to assess gyral pattern, are being investigated in focal epilepsy and may have a role in clinical diagnosis. Characteristics of common and less common developmental and acquired epileptogenic lesions will be demonstrated. Integrating clinical information and functional imaging data improves detection of subtle MRI lesions.

References

1.Lapalme-Remis S, Cascino GD. Imaging for adults with seizures and epilepsy. Continuum (Minneap Minn) 2016;22:1451–79. doi: 10.1212/CON.0000000000000370. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Appropriate Use of Amyloid Positron Emission Tomography and Imaging Dementia - Evidence for Amyloid Scanning Study

Kirk Frey ¹

With the recent development and regulatory approvals of several fluorine-18 labeled amyloid tracers, it is now feasible to apply this technology to clinical practice settings. Recent reviews and summaries of the performance, specificity and sensitivity of PET amyloid imaging together with clinic-pathologic comparisons confirms several important caveats in the clinical use of amyloid imaging. All of the approved tracers have undergone pathologic verification in postmortem studies, indicating that “positive” PET scans correspond to the pathologic presence of moderate-to-high brain levels of fibrillary amyloid deposition. However, in clinical research series, this scan appearance is not limited to subjects with dementia or cognitive impairment, and has an age-related prevalence. Longitudinal series indicate that subjects with “positive” amyloid scans are at increased risk for development of cognitive impairment and dementia. It is not yet known, however, that all subjects with positive scans will eventually develop neurodegenerative dementia. Furthermore, “positive” amyloid scans are not diagnostic of Alzheimer disease; they may be seen frequently also in patients with Lewy body dementias. Recognizing these limitations, appropriate use guidelines have been developed, identifying subjects who may diagnostically benefit from PET amyloid scanning. In the USA, the Centers for Medicare & Medicaid Services has determined that prospective information on the impact of amyloid PET imaging on patient management and outcome is required prior to a decision on coverage. The Imaging Dementia - Evidence for Amyloid Scanning (IDEAS) Study is underway to address these issues, and has completed the recruitment and scanning of over 18,000 patients. Preliminary findings will be discussed.

The aims of the presentation are:

To understand incidence and significance of “positive” amyloid imaging
To review SNMMI appropriate use criteria for amyloid imaging
Understand amyloid imaging characteristics in cognitive disorders
Review rationale and aims of the IDEAS study.

References

1.Barthel H, Sabri O. Clinical use and utility of amyloid imaging. J Nucl Med. 2017;58:1711–7. doi: 10.2967/jnumed.116.185017. [DOI] [PubMed] [Google Scholar]
2.Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, et al. Appropriate use criteria for amyloid PET: A report of the amyloid imaging task force, the society of nuclear medicine and molecular imaging, and the Alzheimer's association. J Nucl Med. 2013;54:476–90. doi: 10.2967/jnumed.113.120618. [DOI] [PubMed] [Google Scholar]
3.Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA. 2015;313:1924–38. doi: 10.1001/jama.2015.4668. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: A meta-analysis. JAMA. 2015;313:1939–49. doi: 10.1001/jama.2015.4669. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Update on Synaptic Neuroimaging: Neuroreceptors and Transporters

Kirk Frey ¹

Since the introduction of molecular neuroimaging, a variety of imaging targets associated with specific neurochemical aspects of neurotransmission have been identified, and methods developed for their imaging depiction. Current status of available markers for presynaptic and postsynaptic specializations will be reviewed, and examples of research applications provided. Amongst the unique contributions of in vivo neurochemical imaging, the ability to detect endogenous effects of synaptic neurotransmitter levels on the basis of competition with radioligands targeting receptor sites will be discussed. Measures of synaptic density and integrity, on the basis of vesicular neurotransmitter transporter imaging, will be reviewed. Tracers and imaging targets with potential clinical application will be presented.

The aims of the presentation are:

To understand types of neurochemical synaptic molecular imaging targets
Appreciate potential roles of targeted synaptic imaging
Understand use of receptor imaging for synaptic neurotransmitter level assessment
Describe current synaptic imaging tracers for clinical evaluations.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Neuroinflammation and New tracers for Neuroscience

Michael Kassiou ¹

Irrespective of the phenotype, e.g. Alzheimer’s disease (AD), Parkinson’s disease (PD) or schizophrenia, the most consistent finding in brain diseases is pronounced changes in the functional state of microglia – the cells responsible for immune defence in the CNS. The translocator protein (TSPO) and the purinergic P2X7 receptor are overexpressed in microglia and are known to modulate their function. Targeting these proteins through the discovery of novel molecules and PET imaging promises to provide a new strategy for treatment of brain disease.

Reference

1.Wilkinson SM, Barron ML, O'Brien-Brown J, Janssen B, Stokes L, Werry EL, et al. Pharmacological evaluation of novel bioisosteres of an adamantanyl benzamide P2X7 receptor antagonist. ACS Chem Neurosci. 2017;8:2374–80. doi: 10.1021/acschemneuro.7b00272. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

F-18 FP-CIT Positron Emission Tomography in Parkinson’s Disease and Atypical Parkinsonism

Jae Seung Kim ¹

Atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), which account for a significant proportion of parkinsonian cases, exhibit drug resistance and fatal neurodegenerative course. Therefore, it is important to make an accurate diagnosis not only for deciding treatment regimens and assessing prognosis, but also for developing new therapeutic strategies. The use of F-18 FP-CIT PET after marketing approval from the KFDA in 2008 is rapidly increasing in Korea for clinical and research purposes because F-18 FP-CIT PET/CT has several advantages over clinical imaging in terms of spatial resolution, imaging time, patient preparation and attenuation correction compared to other DAT imaging such as DAT SPECT. Subregional analysis of striatal F-18 FP-CIT uptake and dual-phases PET imaging technique are useful for detecting a decrease in striatal DAT in parkinsonian patients and distinguishing APD such as PSP and MSA from Parkinson’s disease.

References

1.Oh M, Kim JS, Kim JY, Shin KH, Park SH, Kim HO, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. J Nucl Med. 2012;53:399–406. doi: 10.2967/jnumed.111.095224. [DOI] [PubMed] [Google Scholar]
2.Han S, Oh M, Oh JS, Lee SJ, Oh SJ, Chung SJ, et al. Subregional pattern of striatal dopamine transporter loss on 18F FP-CIT positron emission tomography in patients with pure akinesia with gait freezing. JAMA Neurol. 2016;73:1477–84. doi: 10.1001/jamaneurol.2016.3243. [DOI] [PubMed] [Google Scholar]
3.Kim HW, Kim JS, Oh M, Oh JS, Lee SJ, Oh SJ, et al. Different loss of dopamine transporter according to subtype of multiple system atrophy. Eur J Nucl Med Mol Imaging. 2016;43:517–25. doi: 10.1007/s00259-015-3191-6. [DOI] [PubMed] [Google Scholar]
4.Jin S, Oh M, Oh SJ, Oh JS, Lee SJ, Chung SJ, et al. Additional value of early-phase 18F-FP-CIT PET image for differential diagnosis of atypical parkinsonism. Clin Nucl Med. 2017;42:e80–7. doi: 10.1097/RLU.0000000000001474. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Frontotemporal Dementia-Imaging and Clinical Updates

Samantha Loi ¹

Frontotemporal dementia (FTD) is the most common dementia presenting in people aged under 65 years old. Its clinical presentation is different compared to Alzheimer’s dementia and can be mistaken for other conditions, such as psychiatric disorders. This talk aims to provide an update of the clinical presentations of FTD and their imaging. A series of case studies will be presented illustrating the different types of FTD (behavioural-variant FTD and the language variants), including their symptoms, relevant investigations and imaging.

References

1.Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77. doi: 10.1093/brain/awr179. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14. doi: 10.1212/WNL.0b013e31821103e6. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Nuclear Medicine Innovation: New Challenges in Patient-Specific Dosimetry of Therapy Radiopharmaceuticals – Cons

Alexander Haug ¹

Great efforts have been made in the recent years in order to improve dosimetry in radionuclide therapy. These efforts have been translated into clinical routine, subsequently with the need for costly scintigraphic measurements for measuring absorbed doses. In order to justify these efforts the impact of dosimetry on radionuclide therapy has to be evaluated carefully. Dosimetry has to have impact on the clinical management of patients. This impact can be avoiding toxicity by establishing organ-specific thresholds or it can be improving efficacy by establishing dose thresholds for response. A recent study has shown that most centers in Europe do not regularly use dosimetry and even lessuse dosimetry to tailor radionuclide therapy in a personalized way. In radioiodine therapy certain improvements in establishing dose-response and dose-toxicity relationships have been achieved. Nevertheless, most centers still use fixed doses for radioiodine therapy of both benign and malignant thyroid diseases. In PRRT of neuroendocrine tumours great efforts for performing dosimetry have been done. However, thresholds for kidney toxicity have not been identified, which might be due to the low incidence of relevant kidney toxicity of ¹⁷⁷Lu-DOTATATE therapy. Also, no correlation between hematotoxicity and dose has been identified. In contrast, a first study points towards a dose-response relationship.[1] For other radionuclide therapies such as ¹⁷⁷Lu-PSMA or radioembolization also no dose-toxicity and dose-response relationships have been established. Despite great efforts and numerous publications no thresholds for toxicity and response have been established. Dosimetry has almost no impact on daily practice. Either future large studies will increase the level of evidence, or, alternatively, dose-escalations studies (as done by big pharma) will establish maximum tolerable doses neglecting individual differences.

Reference

1.Ilan E, Sandström M, Wassberg C, Sundin A, Garske-Román U, Eriksson B, et al. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE. J Nucl Med. 2015;56:177–82. doi: 10.2967/jnumed.114.148437. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

What is “Theranostics” and how will it Change the Role of Nuclear Medicine Physicians in Patient Care?

Rodney Hicks ¹

Nuclear medicine was a treatment modality well before the advent of imaging with application of radioisotopes for the treatment of disease. This started shortly after the discovery of radioactivity with widespread adoption of Ra-226, especially for cutaneous malignancies. P-32 was subsequently used by John Hundale Lawrence as one of the first effective therapies for haematological malignancies in the 1930s, while I-131 became and remains the prototypical treatment of thyroid disorders after being first championed by Saul Hertz and Sam Seidlin over 75 years ago. Bone seeking agents like Sr-89 were recognized to deliver palliative benefit in advanced prostate cancer by Charles Pecher in the 1940s and paved the way for later agents including Sm-153 EDTMP and Ra-223. Initially confirmation of localization of activity in presumed sites of disease involved use of external counting devices but this changed with the advent of the rectilinear scanner, which enabled imaging. Nevertheless, the early history of nuclear medicine remained dominated by physicians with an interest in internal medicine. The development of the gamma camera and subsequent evolution tomographic imaging with SPECT and PET, further enabled by hybrid CT or MRI devices, led to the diagnostic use of isotopes becoming the dominant aspect of nuclear medicine practice with gradual erosion of the involvement of nuclear medicine specialists in direct patient care and a shift towards involvement of radiologists in service provision. Against this trend there has been renewed awareness the ability of radiotracers to identify potential therapeutic targets and to use this information to select patients for, and to monitor the efficacy of targeted therapies using radioisotopes. This process has been termed “theranostics”. A significant factor in the rebirth of therapeutic nuclear medicine has been the development of peptides labelled with Ga-68 and Lu-177. Ga-68 DOTA-octreotate PET/CT and Lu-177 DOTA-octreotate peptide receptor radionuclide therapy (PRRT) provides the modern prototype of the theranostic paradigm. Experience with PRRT has, however, emphasized the need for a more rigorous scientific approach to radionuclide therapy and a re-emerging need for engagement of nuclear medicine physicians in multi-disciplinary care of patients with responsibility for recognizing the impact of co-morbidities in treatment outcomes and a responsibility for recognising and preventing or managing, as appropriate, complications of radionuclide therapy. The future holds promise of wide range of therapeutic options based on diagnostic/therapeutic pairs including I-124/I-131, Cu-64/Cu-67, Sc-43/Sc-47 as well as possible use of alpha-emitting radionuclides like Bi0213 and Ac-225. Quantitative SPECT/CT and PET/CT will be key platform technologies for planning and monitoring such therapy and will realise the true promise of molecular imaging in characterising rather than just finding disease. The nuclear medicine physician of the 21st century should become the true embodiment of the principles of precision medicine.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

What is Radiomics+? Prediction Models based on Convergent Data

Antoine Leimgruber ¹

This presentation will:

Address advances in “predictive analytics”, that is post-acquisition data analysis and prediction model generation for efficient, accurate and personalized patient management.
Appreciate current endeavours to move beyond radiology-based radiomics to a “radiomics+” model that includes molecular and other, non-genetic biomarker information. Medical Imaging generates a large amount of data commonly assessed visually using scientific evidence and expert knowledge combined with a level of clinical patient-specific information. In parallel to that, quantitative methods have been developed in today’s multiple modalities environment, providing morphologic, functional and biological information. Recent advances in data mining of quantitative image features from multi-modality medical imaging data together with powerful image analytic tools have lead to what is known today as “radiomics”. Naturally, radiomics analytic techniques have been welcomed with both enthusiasm and scepticism. The process used in radiomics involves the identification of vast arrays of quantitative parameters within digital images. Storage of such data in structured databases can then be used for data mining to aim at the extraction of specific features that have the differentiating power to detect and stratify each individual profile and expression of a given disease. The major challenge is to integrate radiomics data with clinical, pathological, and genomic information to decode the different types of tissue biology and specificities of the disease with a patient. Among examples, many currently available radiomics studies focus on lung cancer for which the current state of the art is evolving and requires a closer look. These new paradigms in data analysis extend however beyond radiology-based radiomics to “radiomics+” that includes genetic and other, non-genetic molecular biomarker information providing efficient, accurate and personalised patient management. Imaging is indeed not the only field roaming the uncharted territory of large medical datasets. Pathology, liquid biopsy techniques or genetic analyses all provide an increasing number of molecular biomarkers. Oncology is the large port of entry of this trend given the need to tailor an increasingly diverse array of targeted therapies to the specificities of each patient and the history of each cancer within each individual. Many institutions are in the process of developing analytic personalised oncology programs (APOs). Through this prism and early local and wider APO experience, this talk will endeavour to give credit to both the traditional expert visual assessment and the radiomics approach and analyse the challenges ahead. Radiomics and imaging genomics are still in a very early stage and while several promising results have been shown, many technical issues have to find solutions and extensive clinical validation studies are ahead. However, radiomics will play a significant role of performing image genotyping and phenotyping to ensure a privileged position of medical imaging in precision medicine. The combination with other genetic and non-genetic biomarkers in what we refer to as “radiomics+” is certainly the next big step in the development of personalised medicine.

References

1.Lambin P, Leijenaar RTH, Deist TM, Peerlings J, de Jong EEC, van Timmeren J, et al. Radiomics: The bridge between medical imaging and personalized medicine. Nat Rev Clin Oncol. 2017;14:749–62. doi: 10.1038/nrclinonc.2017.141. [DOI] [PubMed] [Google Scholar]
2.Gillies RJ, Kinahan PE, Hricak H. Radiomics: Images are more than pictures, they are data. Radiology. 2016;278:563–77. doi: 10.1148/radiol.2015151169. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Aerts HJ. The potential of radiomic-based phenotyping in precision medicine: A Review. JAMA Oncol. 2016;2:1636–42. doi: 10.1001/jamaoncol.2016.2631. [DOI] [PubMed] [Google Scholar]
4.Aerts HJ. The potential of radiomic-based phenotyping in precision medicine: A Review. JAMA Oncol. 2016;2:1636–42. doi: 10.1001/jamaoncol.2016.2631. [DOI] [PubMed] [Google Scholar]
5.Acharya UR, Hagiwara Y, Sudarshan VK, Chan WY, Ng KH. Towards precision medicine: From quantitative imaging to radiomics. J Zhejiang Univ Sci B. 2018;19:6–24. doi: 10.1631/jzus.B1700260. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Sharing is Caring: On the need of Open Research Data

Osman Ratib ¹

The rapid developments of social networks and of cloud-based data storage services have radically changed the way we deal with communication and data management in our daily life. Regarding medical data, such open sharing services face some restrictions and raise ethical and confidentiality issues as well as legal issues regarding the use of these data for research and education. Off-site storage of medical images is not new; several vendors have offered such services for decades already as part of their commercial solutions. What has really changed these recent years is the emergence of such services for the wide public offering very attractive solutions at a very low cost. In medical applications however, such systems must comply with strict regulations and guidelines geared toward protecting patient confidentiality and data security. Medical imaging is becoming a major component of the data required in every medical decision in diagnostic, assessment of treatment response, follow-up of disease recurrence but also in support for surgery. The wealth of data acquired in clinical routine these days is overwhelming and has not been apprehended yet. The rapid evolution of machine learning and deep data-mining tools can potentially open the road to new generation of “radiomics” tools. The main limiting factor of the development of these new analysis techniques is the lack of sufficiently large sets of structured and well-documented imaging data. There is also major difficulties in the ability to collect these large sets of imaging data primarily because the overwhelming regulatory constraints and data protection rules that prevent the usage and exploitation of existing imaging data without formal patient approval. Our presentation will focus on the specific issue of gathering and collecting medical images for the development of large Big-Data repositories for scientific research and review existing initiatives for addressing all the limiting factors that prevent their wide development today.

References

1.Morris MA, Saboury B, Burkett B, Gao J, Siegel EL. Reinventing radiology: Big data and the future of medical imaging. J Thorac Imaging. 2018;33:4–16. doi: 10.1097/RTI.0000000000000311. [DOI] [PubMed] [Google Scholar]
2.Obermeyer Z, Emanuel EJ. Predicting the future - big data, machine learning, and clinical medicine. N Engl J Med. 2016;375:1216–9. doi: 10.1056/NEJMp1606181. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Next Stage in Data Processing: The Future of Quantitative Spect in Clinical Nuclear Medicine

Kathy Willowson ¹

Quantitative SPECT has recently moved from the domain of in-house application to vendor supported production. The ability to perform quantitative SPECT and its role in clinical nuclear medicine is expanding, leading to potential impact on clinical management and standard imaging protocols. This presentation aims to summarise the essential processes involved in quantification of SPECT data and how these are managed by current SPECT hardware and software technology. Future trends in data processing as well as image analysis techniques specific to quantitative assessment will be discussed. An overview of the expected impact that standardisation of quantitative SPECT will have on clinical nuclear medicine will be discussed, including examples of existing quantitative applications and their known issues, speculation on future applications, and the impact it may have impact on clinical work flow and patient management. Quantitative SPECT has a bright future in nuclear medicine, particularly in light of the current trend toward targeted radionuclide therapy and patient specific dosimetry and management. It is likely that in the near future the addition of SPECT quantification will impact on standard clinical nuclear medicine practice and play a positive role in expanding our ability to both diagnose and treat disease.

References

1.Bailey DL, Willowson KP. Quantitative SPECT/CT: SPECT joins PET as a quantitative imaging modality. Eur J Nucl Med Mol Imaging. 2014;41(Suppl 1):S17–25. doi: 10.1007/s00259-013-2542-4. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Medico-Economics of New Targeted Personalized Therapeutics

Richard Zimmermann ¹

Nuclear medicine industry is now fully mature and able to answer to (almost) any technical and regulatory needs and constraints. The few remaining gaps will be presented. Over the past fifty years a kind of natural selection has driven the market to specific medical targets. However, alike any other pharmaceutical business, the future of nuclear medicine will be motivated by economics rather than science: radionuclides, radiopharmaceuticals and technologies with the highest chances of success will be discussed. The development of new radiopharmaceuticals will be limited by access to radionuclides, sizes of production networks, implementation of reliable logistics and potential reimbursement. Conventional pharmaceutical industry has now recognized the interest in radiopharmaceuticals in particular through personalized/precision medicine. Impacts on research topics (stronger selection) and development programs (higher budget) will lead to drastic changes in the very near future that will be highlighted. As a consequence, the overall value of the nuclear medicine segment will dramatically increase, impacting also the future role of researchers and physicians. These changes depending upon local regulation will be addressed as well.

References

1.Zimmermann RG. Why are investors not interested in my radiotracer?The industrial and regulatory constraints in the development of radiopharmaceuticals. Nucl Med Biol. 2013;40:155–66. doi: 10.1016/j.nucmedbio.2012.10.012. [DOI] [PubMed] [Google Scholar]
2.Zimmermann R, Goethals PE. Report Opportunities in Nuclear Medicine –Part I: Radionuclides and Radiopharmaceuticals. 4th ed. MEDraysintell; 2017. [Last accessed on 2018]. p. 1087. Available from: http://www.medraysintell.com . [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Oncology: Colorectal Carcinoma: Treat with the Experts-Regional treatment with ⁹⁰Y-SIRspheres

Elizabeth Bernard ¹

SIRT (Selective Internal Radiation therapy) for liver dominant colorectal carcinoma hepatic metastatic (mCRC) disease is safe and effective when SIR-Spheres are delivered with a multi-disciplinary team approach to treatment planning:

-with the right intent

-to the right location

-in the right dose for the individual patient

Achieving this is dependant an individualised approach to each patient, with a combination of careful clinical and imaging workup. This session will aim to illustrate the steps on the treatment pathway in patients with hepatic metastatic disease from colorectal cancer, including the following:

-Clinical assessment

-Imaging work up

-MDT review-Radiology and Nuclear Medicine

-Treatment planning and dose prescription

-Post-therapy Y90 PET/CT

-Follow up imaging for assessment of treatment response

Several case examples will demonstrate this treatment process in mCRC and our experience at Royal North Shore Hospital will be described.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

A Clinical Overview of Neuroendocrine Tumours

David Chan ¹

Outline: Neuroendocrine tumours (NETs) are a group of uncommon, heterogeneous neoplasms. They exhibit a wide range of biological behaviour and treatment varies considerably depending on the primary site and grade of the tumour. This talk aims to provide a clinical overview of NETs, including the epidemiology and classification of neuroendocrine tumours. The place of multidisciplinary management and systemic therapy options are also discussed to give context to the subsequent presentations regarding NET nuclear medicine in this session.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography in Neuro-oncology

Roslyn Francis ¹

Glioma is the most common primary brain tumour, and is associated with significant morbidity and poor overall survival. Imaging has a key role in the management of primary brain tumours in assisting diagnosis, treatment planning, monitoring treatment response and detection of disease recurrence. MRI has been the mainstay of imaging in primary brain tumours however there are challenges, particularly in the post therapy setting. Metabolic imaging with FDG PET showed initial promise but there are limitations from high background brain activity. Recently there has been increasing evidence for the utility of amino acid PET tracers in glioma, in particular in identifying extent of disease and in assessment of disease recurrence. The potential role of amino acid PET imaging in glioma will be explored and areas of future research and development will be discussed.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Sentinel Lymphoscintigraphy in Breast Carcinoma

Francesco Giammarile ¹

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node (LN) staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. Sentinel lymph nodes (SLNs) are the regional nodes that directly drain lymph from the primary tumour, thus, the first nodes to potentially receive the seeding lymph-borne metastatic cells. SLN mapping and biopsy have become routine techniques in breast cancer management, contributing to development of less invasive surgical procedures. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but SLN biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic and micrometastatic disease in regional lymphatic nodes. The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology, and pathology. Despite the widespread application of SLN biopsy for early-stage breast cancer, there is significant variation in performance characteristics reported for such procedures. Controversies exist with regard to the particle size of the radiotracer, the optimal route for injection, timing and type of scintigraphy and intraoperative detection, and whether or not extra-axillary LNs should be considered for harvesting and analysis. The specific radiotracer and technique used are additionally guided by local availabilities, regulations, and practices. The range of rates for false-negative findings and for SLN identifications emphasize the variability of this procedure. Learning curves for this technical procedure also vary. Nevertheless, once a multidisciplinary team is experienced with the procedure, reasonable levels of accuracy are achieved, with identification rates of more than 95% reported routinely.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Molecular Imaging of Response in Cancer Patients

Rodney Hicks ¹

To the existing pillars of therapeutic oncology, immunotherapy has become the latest addition. Despite relatively low response rates in all but a handful of malignancies, it has gained huge public attention because of sometimes remarkable responses in patients who have failed all other available therapies and particularly because some of these patients appeared to be cured. These “Lazarus” examples have created a rhetoric that immunotherapy is a miracle cure and have fast-tracked approval of therapies in a widening spectrum of indications, including the possibility of its adjuvant use in high-risk malignancies. The use of immunotherapy comes, however, at significant cost, not only related to the agents themselves but also because they induce a wide array of immune-related toxicities that can themselves be extremely expensive to manage. Identification of non-responders early during treatment could minimize the financial and health impact of ineffective therapy while early recognition of immune-related toxicity could preempt serious and sometimes life-threatening complications. Conventional imaging with CT and MRI has been recognized to be suboptimal for early response assessment with attempts to adapt criteria to compensate for these failings. The role of molecular imaging, particularly the use of FDG PET/CT has recently come into focus but is similarly challenged by the unique nature of the mechanism of response to immunotherapy. For nuclear medicine specialists, it is important to understand that the two broad classes of immunotherapy, anti-CTLA4 and Anti-PD-1/PDL-1 agents, have different mechanisms of action with the former acting primarily on the afferent limb of immune response to expand and recruit immune cells to tumour, whereas the latter enhance immune-cell killing by diminishing immune checkpoints. Accordingly, the former can lead to a transient increase in metabolic activity, sometimes referred to as pseudoprogression, whereas the latter generally leads to a reduction in activity if tumour cells are being cleared. Similarly, immune-related complications of therapy are manifold and more common with anti-CTLA4 agents than with anti-PD-1/PDL-1 agents. The increasing use of these classes of immunotherapy further complicates matters. Nevertheless, there are patterns of abnormality that can differentiate pseudoprogression from true progression on FDG PET/CT and that are also characteristic of immune complications and that make this technique a useful adjunct to therapeutic response assessment. Novel agents are emerging that may further enhance the role of molecular imaging not only in monitoring response but also potentially in selecting patients for treatment with these agents.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The role of Positron Emission Tomography Imaging in Neuroendocrine Tumours

Grace Kong ¹

Somatostatin receptor (SSTR) imaging provides assessment of somatostatin receptor status of neuroendocrine tumours (NETs), which is highly expressed in majority of NETs. SSTR imaging plays an important role in tumour staging, preoperative imaging and restaging, for which ⁶⁸Ga-DOTA-somatostatin analog PET/CT is becoming increasingly available as a superior diagnostic technique compared to SSTR scintigraphy. SSTR imaging is also used to determine suitability for peptide receptor radionuclide therapy (PRRT) based on the degree of radiotracer uptake in the tumour. The role of ¹⁸FDG PET/CT is to characterise disease phenotype, and provides useful assessment for high Grade 2 or Grade 3 NETs which generally have higher glucose metabolism, and additionally provides prognostic information. In this session, the aims are to provide an overview of the rationale and evidence of ⁶⁸Ga-DOTA-somatostatin analog PET/CT and ¹⁸FDG PET/CT in patients with NETs, including their role in assisting with theranostics or treatment planning.

Educational objectives:

To describe normal patterns, pearls and pitfalls in interpretation of ⁶⁸Ga-DOTATATE PET/CT
To discuss the clinical diagnostic utility of PET imaging in neuroendocrine tumours
The role of PET imaging in theranostics/treatment planning.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

C-11 Acetate and F-18 Fluoro-2-Deoxyglucose Positron Emission Tomography/Computed Tomography for Hepatocellular Carcinoma Research

Seong Young Kwon ¹

There have been many studies to evaluate clinical values of F-18 FDG and C-11 acetate PET/CT in patients with hepatocellular carcinoma (HCC). In this session, I will review the prognostic value of F-18 FDG PET/CT in patients with HCC based on retrospective multicenter studies supported by the Clinical Trial Network Program of the Korean Society of Nuclear Medicine. In addition, diagnostic performance of two tracers was compared according to metastatic sites in the aspect of tumour microenvironment.

References

1.Hyun SH, Eo JS, Lee JW, Choi JY, Lee KH, Na SJ, et al. Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with barcelona clinic liver cancer stages 0 and A hepatocellular carcinomas: A multicenter retrospective cohort study. Eur J Nucl Med Mol Imaging. 2016;43:1638–45. doi: 10.1007/s00259-016-3348-y. [DOI] [PubMed] [Google Scholar]
2.Yoo SW, Kim DY, Lee C, Min JJ, Kwon SY. Small bowel metastasis from hepatocellular carcinoma detected by 18F-FDG PET/CT but not by 11C-acetate PET/CT. Clin Nucl Med. 2017;42:966–7. doi: 10.1097/RLU.0000000000001882. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

F18-Fluoro-2-Deoxyglucose Positron Emission Tomography/Computed Tomography in Lung Cancer

Eddie Lau ^1,^2,^3,^4,⁵

This presentation will primarily discuss the roles of Hybrid Positron Emission Tomography/Computed Tomography (PET/CT) with F18-fluoro-2-deoxyglucose (FDG) in the evaluation of pulmonary nodules and staging of non-small cell Lung Cancer (NSCLC), as well as touching on the values of FDG PET in prognostic stratification, biopsy guidance, treatment planning and therapeutic monitoring of NSCLC. The key advantages of FDG PET/CT in the assessment of pulmonary nodules and staging of NSCLC will be discussed, as well as the limitations of FDG PET/CT in this clinical setting. A selected case series of FDG PET/CT will be presented to illustrate the potential interpretative pitfalls of FDG PET/CT in the assessment of suspected or proven lung cancer. Staging by FDG PET/CT is critical in determining operability and treatment selection in NSCLC. It is also useful in the planning of biopsy and treatment delivery especially in radiotherapy, as well as providing information in therapeutic monitoring following chemo-radiation and patient prognosis. There are however limitations and pitfalls that need to be recognised to avoid mis-interpretation.

References

1.Hicks RJ, Lau E, Alam NZ, Chen RY. Imaging in the diagnosis and treatment of non-small cell lung cancer. Respirology. 2007;12:165–72. doi: 10.1111/j.1440-1843.2006.01012.x. [DOI] [PubMed] [Google Scholar]
2.Lee WK, Lau EW, Chin K, Sedlaczek O, Steinke K. Modern diagnostic and therapeutic interventional radiology in lung cancer. J Thorac Dis. 2013;5(Suppl 5):S511–23. doi: 10.3978/j.issn.2072-1439.2013.07.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Lau WF, Ware R, Herth FJ. Diagnostic evaluation for interventional bronchoscopists and radiologists in lung cancer practice. Respirology. 2015;20:705–14. doi: 10.1111/resp.12518. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography/Computed Tomography and Positron Emission Tomography/Magnetic Resonance Imaging in Gynaecological Carcinoma

Annika Loft ¹

The impact of FDG PET/CT in Oncology has been increasing through the past many years. The method is valuable also for malignant gynecological diseases for initial diagnostic purposes, staging and treatment decision making. The major drawback of FDG is it being non-specific in the sense of detecting malignancy. In spite of this, the high sensitivities and often relative high specificities of FDG PET/CT makes this imaging method a very valuable tool. For cervical cancer, FDG PET/CT has its’ impact in the staging procedure as a supplement to the clinical FIGO staging due to the possibility of detecting para-aortal lymph node metastases as well as distant metastatic disease and assisting the oncologists when planning radiotherapy for these patients. In patients with a pelvic mass, FDG PET/CT is increasingly used for diagnostic purposes with high sensitivity and specificity in detecting ovarian cancer. In the same procedure it is possible to assess the spread of disease which is mandatory to acknowledge before deciding whether the patient should be offered surgery or neo-adjuvant chemotherapy. PET/MRI is the new kid on the block and the possibilities for increasing knowledge for gynecological malignancies with this method should be exploited.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Contribution of Molecular Imaging to Radiotherapy Planning in Head and Neck Cancer

Michael McKay ¹

Modern radiotherapy (RT) is becoming increasingly conformal, that is, conforming to the three-dimensional shape of RT tumour target volumes. This necessarily involves sharp dose falloffs between the target and surrounding non-target normal tissues, with a requirement for the clearest possible tumour delineation. PET/CT metabolic imaging has a key and evolving role in such target volume selection and delineation. Here we summarise the present and evolving status of PET/CT in the radiotherapy planning of squamous cell cancers the head and neck. For cancers of the head and neck, PET/CT is complimentary to structural imaging modalities not only in delineating primary tumours but also often reveals previously undiagnosed regional nodal disease. At some head and neck subsites, PET/CT is confirmed to enable target size reduction compared to structural imaging alone, with enhanced normal tissue sparing and potentially allowing dose escalation (reviewed in 1,2). These contributions often dramatically affect RT treatment strategies. However, there are some limitations to the use of FDG-PET in RT planning, including its relatively poor spatial resolution and partial voluming effects for small tumours. For cancer of the head and neck RT planning, there is an established role for a contribution from FDG-PET/CT metabolic imaging, as well as exciting new applications for the use of non-FDG metabolic markers.

References

1.Grégoire V, Thorwarth D, Lee JA. Molecular imaging-guided radiotherapy for the treatment of head-and-neck squamous cell carcinoma: Does it fulfill the promises? Semin Radiat Oncol. 2018;28:35–45. doi: 10.1016/j.semradonc.2017.08.003. [DOI] [PubMed] [Google Scholar]
2.McKay M, Taubman K, Faroudi F, et al. Molecular imaging for radiotherapy planning of adult cancers: Current status and expanding applications. Int J Radiat Oncol Biol Phys. 2018 doi: 10.1016/j.ijrobp.2018.03.013. In press. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Clinical Utility of F18-Fluoro-2-Deoxyglucose Positron Emission Tomography/Computed Tomography in Gastric Cancer

Yuji Nakamoto ¹

Gastric cancer is the fifth most common cancer (951,000 cases) and the third leading cause of cancer-related death (723,000 deaths) worldwide in 2012. The overall incidence is decreasing over the last several decades; however gastric cancer is still one of the major malignant neoplasms that can be fatal. Clinical utility of PET/CT using ¹⁸F-fluorodeoxyglucose is reviewed. There is a clear geographical variation in incidence, which is the highest in eastern Asia. Risk factors for gastric cancer include Helicobacter pylori infection, smoking, alcohol, and excess dietary salt. According to Lauren histological classification, there are two main subtypes; intestinal type and diffuse type, characterized by the presence or absence of intercellular adhesion molecules, respectively. Complete surgical resection is considered the only curative treatment; thus early diagnosis is important to improve the prognosis. The primary method to detect and diagnose gastric cancer is endoscopy, and generally CT is used for the evaluation of metastasis. For gastric cancer, no clear benefits of FDG-PET have been identified in the detection of gastric cancer, because sensitivity is quite low due to several factors, e.g. small lesion, histological non-avidity, physical uptake of gastric wall. However, some investigators indicate that PET can improve the detection of metastatic disease, and the use of PET for the detection of occult metastasis is suggested in several clinical guidelines (National Comprehensive Cancer Network and the European Society for Medical Oncology). In post-operative restaging, PET/CT is occasionally useful, as it is recognized in other malignancies. FDG-PET/CT can be applicable and helpful for detecting unexpected metastases and/or inconclusive recurrence in patients with gastric cancer.

References

1.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. doi: 10.1002/ijc.29210. [DOI] [PubMed] [Google Scholar]
2.Wu CX, Zhu ZH. Diagnosis and evaluation of gastric cancer by positron emission tomography. World J Gastroenterol. 2014;20:4574–85. doi: 10.3748/wjg.v20.i16.4574. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Radioimmunotherapy of Lymphoma: Past, Present and Future

Richard Wahl ¹

This lecture will:

a)
Review clinical experience with treatment of NHL and HD with radioimmunotherapy at non-myeloablative doses as a salvage, consolidation, and as initial primary treatment;
b)
Review clinical experience with dosimetry-driven (planar and SPECT) RIT at myeloablative doses for recurrent disease;
c)
Examine the potential roles of next generation radioimmunotherapies with fully human antibodies and alternative radioisotopes;
d)
Highlight new follow-up data in NHL patients treated with RIT

Radioimmunotherapy with Anti CD-20 has shown excellent anti-tumour activity in several settings including in the initial treatment, consolidation and recurrent tumour settings. Newer antibodies may allow more innovative therapy approaches including with alpha emitters and alternative beta emitters.

References

1.Yoon JT, Longtine MS, Marquez-Nostra BV, Wahl RL. Evaluation of next-generation anti-CD20 antibodies labeled with zirconium 89 in human lymphoma xenografts. J Nucl Med. 2018:pii: jnumed.117.203299. doi: 10.2967/jnumed.117.203299. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, et al. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus 131I-tositumomab: Long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018;36:697–703. doi: 10.1200/JCO.2017.74.5083. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Barr PM, Li H, Burack WR, LeBlanc M, Smith SM, Gopal AK, et al. R-CHOP, radioimmunotherapy, and maintenance rituximab in untreated follicular lymphoma (SWOG S0801): A single-arm, phase 2, multicentre study. Lancet Haematol. 2018;5:e102–8. doi: 10.1016/S2352-3026(18)30001-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Gordon LI. Consolidation and maintenance in follicular lymphoma: Radioimmunotherapy revisited?Lancet Haematol. 2018;5:e96–7. doi: 10.1016/S2352-3026(18)30015-2. [DOI] [PubMed] [Google Scholar]
5.Green DJ, Shadman M, Jones JC, Frayo SL, Kenoyer AL, Hylarides MD, et al. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. Blood. 2015;125:2111–9. doi: 10.1182/blood-2014-11-612770. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Paediatrics: Glomerular Filtration Rate Measurement in Children

Anita Brink ¹

Glomerular filtration rate (GFR) measurement is essential to evaluate renal function in children with renal disease as well as children who receive nephrotoxic medication. The use of Inulin as a tracer to measure GFR is considered the “gold-standard”. This test is technically demanding and the tracer is not readily available and as such; is rarely performed in clinical practice. Radionuclide GFRs using ⁵¹Chromium-ethylenediamine tetraacetic acid (EDTA) or ^99mTc diethylenetriaminepentaacetic acid (DTPA) is used for the measurement of GFR in routine clinical practice. The test is valid in patients down to a GFR of 15ml/min/1.73m². The accuracy and reproducibility of the two sample radionuclide GFR depends on careful attention to technique during the test as well as meticulous quality control of the results obtained. This presentation will focus on a practical everyday approach to performing two sample radionuclide GFR measurements. Special attention will be given to the required quality control steps. The difference in accuracy between measurement of GFRs with the two sample method, one sample method, camera based methods as well as creatinine based nomograms will be illustrated.

References

1.Gates GF. Glomerular filtration rate: Estimation from fractional renal accumulation of 99mTc-DTPA (stannous) AJR Am J Roentgenol. 1982;138:565–70. doi: 10.2214/ajr.138.3.565. [DOI] [PubMed] [Google Scholar]
2.Piepsz A, Colarinha P, Gordon I, Hahn K, Olivier P, Sixt R, et al. Guidelines for glomerular filtration rate determination in children. Eur J Nucl Med. 2001;28:BP31–6. [PubMed] [Google Scholar]
3.Piepsz A, Tondeur M, Ham H. Revisiting normal (51)Cr-ethylenediaminetetraacetic acid clearance values in children. Eur J Nucl Med Mol Imaging. 2006;33:1477–82. doi: 10.1007/s00259-006-0179-2. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Nononcology Uses of Paediatric Positron Emission Tomography/Magnetic Resonance Imaging-Epilepsy and Infection

Peter Francis ¹

The Royal Children’s Hospital Melbourne commenced its PET/MRI service in March 2016. Since this time over 700 paediatric PET/MRI studies have been performed. Greater than 35% of these have been for pre-surgical epilepsy workup and infection/inflammation imaging. We present our experience with these groups to date. We will discuss our imaging protocols, workflow and limitations of our service as well as using clinical cases and imaging findings from our data base to demonstrate outcomes. Greater than 180 PET/MRI epilepsy studies have been performed with a smaller fraction of infection/inflammation studies. The results of this cohort will be presented. The introduction of the PET/MRI service at the Royal Children’s Hospital has allowed greater diagnostic certainty in the pre-surgical workup of paediatric epilepsy patients and allows a more streamlined approach to the imaging of the difficult febrile patient.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography/Computed Tomography in the Evaluation of Uncommon and Rare Paediatric Malignancies

Robert Howman-Giles ^1,^2,³

This presentation will review the application of PET/CT in solid tumours in childhood and adolescence excluding the common malignancies i.e. lymphoma and sarcoma. FDG PET/CT has been shown to play a significant role in the management of these malignancies but there is very little data on the applications in uncommon and rare malignancies in the paediatric and adolescent age groups. In some paediatric common malignancies FDG PET/CT does not play a major role but in certain clinical circumstances PET/CT may have a place (e.g. neuroblastoma and Wilms’ tumour). The basic principle of increased metabolic activity in malignant cells due to up-regulation of glucose transporters also applies in other types of paediatric malignancies. In these uncommon malignancies PET/CT has a major role in the initial staging of malignancy, assessment of response, end of treatment staging and surveillance. Specific malignancies in childhood and adolescence will be discussed including neuroblastoma and neuro-endocrine tumours, Langerhan’s cell histiocytosis, undifferentiated and unclassified tumours, renal, hepatic malignancies, germ cell tumours and carcinomas. Also, theranostic applications with MIBG therapy and more recently somatostatin agents for diagnostic PET CT imaging with Ga68 DOTATATE followed by LUTATE therapy will be discussed. FDG PET/CT has an important role in the management of many malignancies in childhood and adolescence. Even though there is sparse literature in many of the uncommon and rare paediatric malignancies, the same applications of PET/CT still applies i.e improved staging, assessment of therapy response, detection of residual malignancy and metastatic disease, end of therapy staging and surveillance.

References

1.Howman-Giles R, London K, Uren RF. Solid Tumours in Childhood. In: Treves ST, editor. Pediatric Nuclear Medicine and Molecular Imaging. 4th ed. Ch. 23. Springer-Verlag; 2014. pp. 513–40. [Google Scholar]
2.Uslu L, Donig J, Link M, Rosenberg J, Quon A, Daldrup-Link HE, et al. Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies. J Nucl Med. 2015;56:274–86. doi: 10.2967/jnumed.114.146290. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography/Computed Tomography and Positron Emission Tomography/Magnetic Resonance Imaging in the Management of Paediatric Sarcomas

Egesta Lopci ¹

Sarcomas comprise a very heterogeneous group of malignant tumours of mesenchymal origin potentially interesting any part of the human body. Bone localizations represent approximately 20% of the cases and comprise prevalently Osteosarcoma and Ewing’s sarcoma. The current gold standard in tumour detection and local staging of sarcomas is represented by gadolinium enhanced magnetic resonance imaging (MRI). This modality when used in oncologic therapy monitoring and follow-up after treatment remains however challenging. In particular, MRI may not be able to differentiate between residual or recurrent tumour from post-operative or treatment-induced changes. Besides conventional imaging modalities, metabolic imaging with FDG PET/CT has gained increasing importance over the last years for disease staging, restaging and treatment response assessment. This is reflected on the clinical guidelines recommending the use of the modality in the routine assessment of bone sarcomas. Nevertheless, the consolidation of the principal clinical applications requires further evidence and dedicated multicentric trials. Following the success of hybrid imaging with PET/CT, there is increasing interest in the development of integrated PET/MRI systems, combining the highly sensitive molecular imaging capability of PET with the excellent anatomical details, soft-tissue contrast, and functional information of MRI. Scientific and clinical advantages of fully integrated PET/MRI tomographs comprise also the significant reduction of radiation exposure which is of particular relevance in paediatric applications. By combining the two imaging modalities, PET/MRI can be expected to have a higher accuracy than currently available imaging procedures. This advantage is most valuable in particular in sarcomas, where the new device can provide a more accurate TNM-stage, optimize sarcoma management and give a more precise therapy response assessment. The aim of this presentation is to provide a resume on the most relevant applications of PET/CT and PET/MRI in the current clinical context and a glance over future perspectives in bone sarcoma assessment.

References

1.Antoch G, Bockisch A. Combined PET/MRI: A new dimension in whole-body oncology imaging? Eur J Nucl Med Mol Imaging. 2009;36(Suppl 1):S113–20. doi: 10.1007/s00259-008-0951-6. [DOI] [PubMed] [Google Scholar]
2.Costelloe CM, Chuang HH, Madewell JE. FDG PET/CT of primary bone tumors. AJR Am J Roentgenol. 2014;202:W521–31. doi: 10.2214/AJR.13.11833. [DOI] [PubMed] [Google Scholar]
3.ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii113–23. doi: 10.1093/annonc/mdu256. [DOI] [PubMed] [Google Scholar]
4.Franzius C, Sciuk J, Daldrup-Link HE, Jürgens H, Schober O. FDG-PET for detection of osseous metastases from malignant primary bone tumours: Comparison with bone scintigraphy. Eur J Nucl Med. 2000;27:1305–11. doi: 10.1007/s002590000301. [DOI] [PubMed] [Google Scholar]
5.Völker T, Denecke T, Steffen I, Misch D, Schönberger S, Plotkin M, et al. Positron emission tomography for staging of pediatric sarcoma patients: Results of a prospective multicenter trial. J Clin Oncol. 2007;25:5435–41. doi: 10.1200/JCO.2007.12.2473. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography/Magnetic Resonance Imaging of Paediatric Lymphoma

Lisa States ¹

This presentation will review the utility of PET/MR in the management of paediatric lymphoma. Hodgkin lymphoma and non-Hodgkin lymphoma combined are the third most common cancer in children after brain tumours and leukemia. Molecular Imaging with ¹⁸F-FDG PET has become the preferred imaging tool for staging, treatment planning, response to therapy and restaging. Compared with conventional imaging FDG PET has a higher sensitivity for detection of nodal disease and bone marrow metastases. Initial publications have shown PET/MR to be equivalent to PET/CT in the detection of disease. PET/MR has the obvious advantage of decreasing dose and theoretically decreasing second malignancy. A drawback of PET/MR is long acquisition time. This presentation will focus on protocol options for PET/MR and ongoing research to optimize clinical use in the paediatric patient. Diffusion weighted imaging and intravenous contrast will be discussed.

References

1.Kirchner J, Deuschl C, Schweiger B, Herrmann K, Forsting M, Buchbender C, et al. Imaging children suffering from lymphoma: An evaluation of different 18F-FDG PET/MRI protocols compared to whole-body DW-MRI. Eur J Nucl Med Mol Imaging. 2017;44:1742–50. doi: 10.1007/s00259-017-3726-0. [DOI] [PubMed] [Google Scholar]
2.Ponisio MR, McConathy J, Laforest R, Khanna G. Evaluation of diagnostic performance of whole-body simultaneous PET/MRI in pediatric lymphoma. Pediatr Radiol. 2016;46:1258–68. doi: 10.1007/s00247-016-3601-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

I-131 Therapy in Benign Thyroid Disease – Paediatric Experience

Ka Kit Wong ¹

Paediatric hyperthyroidism is a rare but potentially serious condition, with greater than 95% of cases due to Graves’ disease. If unrecognized it can have a wide range of complications and affect the child’s growth and impact school performance. Radioactive iodine therapy (RAIT) is a definitive treatment, as an alternative to surgery, when anti-thyroid medications are ineffective or have intolerable side effects. The use of radioiodine I-131 for treatment of hyperthyroidism has a long history and safety track record, although there are understandable parental concerns regarding radiation exposure in children whom have increased radiation sensitivity and long life expectancy. The longest follow-up of paediatric patients receiving RAIT do not show evidence for secondary cancers. Nonetheless, it is important to have a goal of hypothyroidism and to promptly establish euthyroidism with thyroid hormone replacement, avoiding undertreatment or repeated treatments. It is prudent to avoid RAIT in very young patients less than 5 years of age. Empiric or calculated activity doses of I-131 can be used, although estimations of thyroid size can be challenging in children. Activity doses of at least 5.55 MBq (0.150 mCi) per gram of thyroid tissue should be used. Parents should be counselled on goals of treatment, radiation safety precautions, expected clinical course, possible adverse effects, and alternative treatments. Beta-blockers should be used liberally during the treatment. The treating physician should be aware of pitfalls including thyroid eye disease, thyroid storm, and radiation induced thyroiditis. Lingual thyroid is a rare congenital abnormality presenting with hypothyroidism in neonates and infants that is usually adequately treated with thyroid hormone replacement. Rarely, obstructive symptoms may develop in childhood causing difficulties with swallowing or breathing. We have used RAIT successfully to ablate lingual thyroid to relieve symptoms as an alternative to surgery. SPECT/CT can assist planning of these treatments.

References

1.Okawa ER, Grant FD, Smith JR. Pediatric Graves'disease: Decisions regarding therapy. Curr Opin Pediatr. 2015;27:442–7. doi: 10.1097/MOP.0000000000000241. [DOI] [PubMed] [Google Scholar]
2.Srinivasan S, Misra M. Hyperthyroidism in children. Pediatr Rev. 2015;36:239–48. doi: 10.1542/pir.36-6-239. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Physics: Physics Quantitation: Standardization of Molecular Imaging Data in Clinical Trials

Paul Kinahan ¹

The ability to assay tumour biologic features and the impact of drugs on tumour biology is fundamental to drug development. Clinical trials that test the safety and therapeutic benefit of promising treatments are essential in translating new knowledge into tangible benefits for patients with cancer. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. Advances in quantitative molecular imaging, particularly positron emission tomography (PET) imaging, have enabled quantitative non-invasive molecular assays. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumour biology without perturbing it. The successful use of quantitative imaging biomarkers requires a clear understanding pf the sources of bias and variance, standards, and appropriate use guidelines. These efforts have been facilitated by multiple initiatives, including the SNMMI, EANM, RSNA, QIBA, NIST and others. Combined efforts in these areas makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice.

Disclosure of interest: P Kinahan Conflict with: PET/X LLC, Conflict with: GE Healthcare.

Reference

1.FDG-PET/CT Technical Committee. FDG-PET/CT as an Imaging Biomarker Measuring Response to Cancer Therapy Profile Version 1.15. 2015. [Last accessed on 2018]. Available from: http://www.RSNA.ORG/QIBA .

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Effectively Communicating Radiation Risks: The Toughest Task

Henry D Royal ¹

Even though radiation risks are well known and the radiation risk from diagnostic studies is small, communicating these risks fairly and objectively is very difficult. The linear no threshold hypothesis (LNTH) used for radiation protection purposes is controversial because it leads to misleading statements such as there is no safe level of radiation. The pros and cons of the use of the LNTH will be discussed. A major problem with the communication of risks is that many think that the acceptability of a risk should be related to its magnitude. In fact, other factors are extremely important in determining if a risk is acceptable. These other factors include whether the risk is voluntary, whether it is necessary and whether the person(s) being exposed to the risk is is the same person(s) receiving the benefits. The public can only optimize the use of limited resources to promote general health if these resources are utilized wisely in a way that accounts for the magnitude of the risks and the effectiveness of measures to decrease the risk.

Reference

1.Hall E, Garicia EJ, et al. Radiobiology for the Radiologist. 2012 [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Digital Positron Emission Tomography and improvements in Time-of-Flight Positron Emission Tomography

Suleman Surti ¹

Time-of-Flight (TOF) PET imaging technology was commercially introduced for clinical PET/CT systems in 2006 and has led to significant enhancements in image quality. The improved performance was enabled by technological advancements both in hardware design and software algorithms and has led to both shorter clinical imaging times and improved quantitative images. The talk will be divided into three major sections. First, a review of the principles of TOF PET imaging with a focus on instrumentation, ranging from hardware design to software algorithms. Second, a presentation of data to demonstrate the impact of TOF PET on clinical imaging and examples of new clinical applications that can benefit from utilizing improved TOF performance. Finally, a discussion of the technology that is advancing the hardware design of TOF PET systems, and how these developments have the potential for further improvements in imaging performance. This will include a description of the latest state-of-art digital PET systems that are being introduced by the major vendors.

References

1.Surti S. Update on time-of-flight PET imaging. J Nucl Med. 2015;56:98–105. doi: 10.2967/jnumed.114.145029. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Surti S, Karp JS. Advances in time-of-flight PET. Phys Med. 2016;32:12–22. doi: 10.1016/j.ejmp.2015.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Vandenberghe S, Mikhaylova E, D'Hoe E, Mollet P, Karp JS. Recent developments in time-of-flight PET. EJNMMI Phys. 2016;3:3. doi: 10.1186/s40658-016-0138-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Conti M. Focus on time-of-flight PET: The benefits of improved time resolution. Eur J Nucl Med Mol Imaging. 2011;38:1147–57. doi: 10.1007/s00259-010-1711-y. [DOI] [PubMed] [Google Scholar]
5.Frach T, et al. In IEEE Nuclear Science Symposium and Medical Imaging Conference. Orlando FL: 2009. The digital silicon photomultiplier: Principle of operation and intrinsic detector performance. [Google Scholar]
6.Grant AM, Deller TW, Khalighi MM, Maramraju SH, Delso G, Levin CS, et al. NEMA NU 2-2012 performance studies for the siPM-based toF-PET component of the GE SIGNA PET/MR system. Med Phys. 2016;43:2334. doi: 10.1118/1.4945416. [DOI] [PubMed] [Google Scholar]
7.Miller MA, et al. In Annual Meeting of the Society of Nuclear Medicine. St. Louis Mo: 2014. Initial characterization of a prototype digital photon counting PET system. [Google Scholar]
8.Miller M, et al. Characterization of the vereos digital photon counting PET system. J Nucl Med. 2015;56(Suppl 3):434. [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Quantitative Single Photon Emission Computed Tomography: State of the Art and Current Issues

Kathy Willowson ¹

The acceptance of quantitative SPECT as mainstream vendor-supplied technology has large implications for not only clinical applications, yet also the role of medical physics. This presentation aims to review the essential components of the quantitative algorithm and the current state of the art quantitative ability, as well as the role of both software and hardware developments in SPECT. An overview of acceptable quantitative SPECT validation techniques will be given, including recommendations for incorporation into a standard QC programme. Current issues relating to quantitative acquisition and analysis will be discussed, including possible workarounds and suggestions of analysis techniques. Both current and future applications of quantitative SPECT will be summarised, including potential clinical impact and speculation on further development and incorporation into clinical practice. The time of quantitative SPECT in standard clinical nuclear medicine has arrived. This opens up exciting opportunities for advanced image analysis techniques that may impact on patient management. It is vital that the physicist has a sound understanding of the components of the quantification algorithm and associated issues to ensure correct and effective use and management of quantitative SPECT.

Reference

1.Bailey DL, Willowson KP. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med. 2013;54:83–9. doi: 10.2967/jnumed.112.111476. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Tetrahedral-Mesh Counterparts of International Commission on Radiological Protection Reference Computational Phantoms

Yeon Soo Yeom ^1,²

This talk is to introduce the new adult male and female mesh-type reference computational phantoms (MRCPs) recently developed in the International Commission on Radiological Protection (ICRP), generally discussing their advantages over the current voxel-type reference computational phantoms (VRCPs).[1] The MRCPs were constructed by converting the VRCPs to a high-quality tetrahedral-mesh format and addressing the limitations of the VRCPs mostly due to their limited voxel resolutions. The MRCPs were implemented in Monte Carlo codes (i.e., Geant4, MCNP6, and PHITS) to investigate computation speed and memory usage. In addition, dose coefficients (DCs) of the MRCPs for some external and internal exposures were calculated and compared with the current reference DCs produced with the VRCPs and supplemental stylized phantoms.[2,3] Furthermore, the MRCPs, using their high deformability over the VRCPs, were transformed to phantoms in different statures or postures, which were then used to calculate DCs for industrial radiography sources near the body. The MRCPs include all the target and source regions needed for effective dose calculations, even micron-scale regions of the respiratory and alimentary tract organs, urinary bladder, skin, and eye lens, completely obviating the need of supplemental stylized phantoms. PHITS, compared to Geant4 and MCNP6, showed the best performance in both computation speed and memory usage for the MRCPs, which are even faster than the VRCPs. The DCs of the MRCPs were found to be very similar to the current reference DCs for penetrating radiations (e.g., photons and neutrons), but more reliable for weakly penetrating radiations (e.g., electrons and ions). The DCs for industrial radiography sources were found to be significantly influenced by different statures, demonstrating the capability of the MRCPs for personalized dosimetry. The MRCPs, as the next generation of ICRP reference computational phantoms, are expected to be used in many dosimetry applications, including nuclear medicine dosimetry in the future.

References

1.Menzel HG, Clement C, DeLuca P. ICRP publication 110. Realistic reference phantoms: An ICRP/ICRU joint effort. A report of adult reference computational phantoms. Ann ICRP. 2009;39:1–64. doi: 10.1016/j.icrp.2009.09.001. [DOI] [PubMed] [Google Scholar]
2.Petoussi-Henss N, Bolch WE, Eckerman KF, Endo A, Hertel N, Hunt J, et al. ICRP publication 116. Conversion coefficients for radiological protection quantities for external radiation exposures. Ann ICRP. 2010;40:1–257. doi: 10.1016/j.icrp.2011.10.001. [DOI] [PubMed] [Google Scholar]
3.Desmaris G. Cosmic radiation in aviation: Radiological protection of air France aircraft crew. Ann ICRP. 2016;45:64–74. doi: 10.1177/0146645316636009. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Pulmonary: Displaying and Reporting V/P Single Photon Emission Computed Tomography - State of the Art

Marika Bajc ¹

The aim of the presentation is to demonstrate how to perform and interpret V/P SPECT in patients with suspected pulmonary embolism (PE). There are 19000 patients V/P SPECT studies were performed in our clinical practice for clinically suspected PE since 2002. From 2004 we quantify reduction of ventilation and perfusion, primarily to estimate the extent of PE. Furthermore, we are also interpreting ventilation changes to quantify total preserved lung function and grade severity of obstructivity. In one retrospective study during a period of 2 years, normal finding was observed in 30%, PE in 30% of patients. Among patients not showing sign of PE, ventilation helped to explain perfusion defects of different nature such as obstructive diseases, parenchymal changes as pneumonia and tumour and also heart failure. Additional finding was observed in 39% of patients. Positive predictive value for PE diagnostic was 99 % and negative predictive value was 98% (Bajc at al. J Intern Med 2008). Similar results were observed in another center (Begic at al. Nuclearmedizin 2015). Quantification of the PE extend has an impact on PE treatment. Patients with lung perfusion defects up to 40 % and ventilation defects up to 20 % are treated at home. In a retrospective study from 2007 to 2011, 416 outpatients were diagnosed with acute symptomatic PE. 63 % were treated at home from day 1 one and another 11% from day 2. There was no PE-related mortality on follow up (Elf at al. J Thromb Thrombolysis. 2015). Inverted perfusion gradient allowed diagnosis of left heart failure with a positive predictive value in 88% (Jogi at al. NMC 2008). V/P SPECT is also used for estimation of lung function and phenotype in patients with chronic obstructive pulmonary disease. Distribution of ventilation and perfusion, penetration of Technegas to the periphery allows grading of obstructivity, estimation of the total lung function (Jogi et al. EJNM 2011, Jobse et al. JNM 2013, Bajc et al. Ann Nucl Med 2015, Norberg P et al. EJNMMI Res. 2014). In COPD patients, V/P SPECT frequently identifies comorbidities such as PE, pneumonia, LHF and tumour (Jogi et al. Int J Chron Obstruct Pulmon Dis. 2015, Begic et al. Nuklearmedizin 2015, Bajc et al. Int J Chron Obstruct Pulmon Dis 2017, Nasr et al. EC Pulmonology and Respiratory Medicine 2017). Notably, the standardized technique together with holistic interpretation reduced the rate of non-diagnostic reports to the level below 4 %.(Corbus et al. NMC 1997, Lemb at al Nuklearmedizin 2001, Reinartz et al. JNM 2004, Leblanc et al NMC 2007, Bajc et al. JIM 2008, Gutte et al. JNM 2009, Gruning et al. Clin Imaging 2014). V/P SPECT is a fast procedure that can be performed in any patient, without the burden of contrast and with minimal radiation exposure. It offers a first-hand method for diagnosis of PE. Quantification of PE is of value for the decision of safe outpatient therapy in a majority of patients and for follow up. V/P SPECT is also of value for diagnostics of other diseases such as COPD, left heart failure, and pneumonia. With increasing number of tomographic gamma cameras, V/P SPECT should be applied in each hospital with available standard software.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Challenges in V/P Single Photon Emission Computed Tomography, Continuing after 40 Years

Bjorn Jonson ¹

Ventilation/Perfusion tomography (V/P SPECT) for diagnosis of PEF or diagnosis of PE, V/P SPECT was proposed by Eustace et al. in 1993. In 1997, Corbus et al. presented a large study showing that V/P SPECT provided accurate diagnosis in 96% of patients and with much higher specificity than planar studies. However, planar scintigraphy remained for long the standard method. Perfusion scanning was usually followed by ventilation scanning, sometimes on the following day. In 2000, a method allowing ventilation/perfusion scanning in the reversed order to be performed in one session within one hour using low doses of ^99mTc for both procedures was available. A challenge to do the same thing with V/P SPECT was successfully taken up by Palmer et al, 2001. The method was validated in pigs and in patients and showed to be superior to planar scintigraphy (Bajc et al. 2002, 2004, Reinartz et al. 2004, Gutte et al. 2010, Quirze et al 2014). In 2008, Bajc et al. demonstrated high clinical utility of the method combined with a holistic rather than probabilistic principle of interpretation. These principles for scanning and interpretation were recommended in the guidelines of the European Society of Nuclear Medicine (Bajc et al., 2009, Eur J Nucl Med Mol Imaging). These guidelines are now, in 2018, widely practiced in Europe and are being implemented in other parts of the world, including China and Japan. As shown by recent ‘Use Criteria’ for USA, their Society of Nuclear Medicine is more reluctant to the leave the outdated principles of planar pulmonary scintigraphy (Waxman et al., 2017, J Nucl Med). Myocardial single photon emission tomography was born 40 years ago (Keyes et al. 1978, Holman et al. 1979). This method was pretty soon accepted as superior to planar technique and no vast studies comparing planar imaging with SPECT were asked for. The advantages were evident for all of us who had struggled with excruciating interpretation of hazy planar images. The separation between the myocardium and overlaying and adjacent structures was of fundamental value. The same advantage of SPECT is obvious for the lungs. V/P SPECT for additional diagnoses - during the 70’s and 80’s, it was shown that obstructive disease and pneumonia could be revealed by use of ventilations scans. Heart failure was recognized from reversed perfusion gradient. V/P SPECT performed in patients for suspected PE show in up to 40% of cases additional diagnoses, i.e. more frequently than PE. Examples are COPD, pneumonia, left heart failure, chronic embolism, tumour and other parenchymal processes (Bajc et al. 2008, Begic et al. 2015). The patterns for these diseases are very important to recognize, because these diagnoses may present with similar clinical manifestations as PE and may partly or fully explain the symptoms of the patient. Accordingly, they should be reported. It appears doubtful that this is regularly done. Radiologists often claim that CTPA uniquely offers diagnoses of alternative diseases. Nuclear medicine should refute such nonsense and consequently underline that V/P SPECT is not a method only for PE. V/P SPECT and computer tomography of the pulmonary artery (CTPA) are the two principle imaging modalities by which PE can be diagnosed. Both fulfil basic requirements for diagnosis of PE. V/P SPECT is often not available. CTPA is often contraindicated. V/P SPECT and CTPA are both indispensable. Continuing challenges for Nuclear Medicine - How can we best promote the rational use of V/PSPECT? By education, training and research! Nuclear medicine is a small discipline. Future diagnostics will partly be based upon artificial intelligence. That will in the long run reduce costs and increase quality. To be prepared, we need to collect colossal amounts of information. Broad multidisciplinary research is a mandatory component in our efforts to gain motivated impact.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Computed Tomography Pulmonary Angiography - The Good, the Bad and the Ugly

Diane Pascoe ¹

CTPA is a sensitive and specific test for the diagnosis of pulmonary embolism, but so too is VQ. How can we decide which test to use in a given clinical scenario? The inherent strengths and weaknesses of CTPA, particularly as compared with VQ, will be discussed. This will include an explanation of the CTPA technique and how it can contribute to false positives, false negatives and non-diagnostic studies. Over-diagnosis with CTPA is a somewhat controversial but increasing concern, and will also be addressed, as it may place patients at risk of complication due to overtreatment.

Reference

1.Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: Evidence of overdiagnosis. Arch Intern Med. 2011;171:831–7. doi: 10.1001/archinternmed.2011.178. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

V/Q Single Photon Emission Computed Tomography and Single Photon Emission Computed Tomography/Computed Tomography Imaging

Paul Roach ¹

To demonstrate the utility of planar, SPECT and SPECT/CT imaging for the investigation of patients with suspected pulmonary embolism (PE), the practicalities, advantages and disadvantages of planar, SPECT and SPECT/CT imaging were reviewed. Planar ventilation-perfusion (V/Q) scanning is often used to investigate pulmonary embolism, however it has well-recognized limitations. SPECT overcomes many of these through its ability to generate 3-dimensional imaging data. V/Q SPECT has higher sensitivity, specificity and accuracy than planar imaging and a lower indeterminate rate. It can also facilitate new ways of displaying and analyzing data, such as with parametric V: Q ratio images. V/Q SPECT can be further enhanced by the addition of CT data, typically using a low dose CT scan performed on a hybrid SPECT/CT scanner. Hybrid imaging has been shown to improve specificity and overall accuracy of V/Q scintigraphy as well as facilitating more accurate clot localisation. With the increased availability of hybrid SPECT/CT scanners in many Nuclear Medicine departments, such an approach can be implemented in most centres with little additional acquisition time or radiation dose. In 2018, V/Q scintigraphy should be performed with SPECT, and in most patients, SPECT/CT to optimise diagnostic accuracy. SPECT is superior to planar imaging.

Reference

1.Roach PJ, Schembri GP, Bailey DL. V/Q scanning using SPECT and SPECT/CT. J Nucl Med. 2013;54:1588–96. doi: 10.2967/jnumed.113.124602. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Where to Now for the V/Q Scan - US Perspective: Past, Present and Future

Henry D Royal ¹

VQ imaging for the diagnosis of pulmonary embolism was extensively studied in the United States in the late 1980s. This test was the non-invasive test of choice for the diagnosis of pulmonary embolism until computed tomography pulmonary arteriography (CTPA) was introduced in the 2000s. The number of nuclear medicine studies performed in the United States continued to grow each year until the mid 2000s. Since that time, economic pressures have decreased the number of nuclear medicine studies by about 30%. Additional pressure from CTPA, have reduced the number of VQ studies by a greater percentage. The US has been slow to adopt SPECT and SPECT/CT VQ imaging in part because it is one of the few countries where Technegas™ has not been approved for human use. Renewed efforts to get Technegas™ approved in the United States are underway. If successful, use of VQ SPECT and SPECT/CT will likely increase. The combination of functional and anatomic imaging provided by the use of VQ SPECT/CT will surely increase the value of VQ imaging.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

V/Q Single Photon Emission Computed Tomography - Artefacts, Pearls, Pitfalls and Interactive Cases

Geoffrey Schembri ¹

The presentation will cover common normal variants in V/Q scanning with particular focus on SPECT artefacts. Unusual pathologies will also be presented using interactive case presentations.

Reference

1.Schembri GP, Roach PJ, Bailey DL, Freeman L. Artifacts and anatomical variants affecting ventilation and perfusion lung imaging. Semin Nucl Med. 2015;45:373–91. doi: 10.1053/j.semnuclmed.2015.02.009. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging of PE in Pregnancy

Geoffrey Schembri ¹

To cover relevant issues in the imaging of PE in pregnancy. The presentation will cover issues relevant to PE diagnosis including: patient-related factors affecting the technical quality of imaging modalities, radiation dosimetry for the mother and foetus, and protocol variations.

Reference

1.Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med. 2010;40:442–54. doi: 10.1053/j.semnuclmed.2010.07.007. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Radiopharmaceutical Sciences: New Chelators for Targeted Alpha-Therapy: The Chemistry Driving Efficacy and Safety

Rebecca Abergel ¹

Among strategies developed to improve the effectiveness and minimize the consequences of radiotherapy, targeted alpha therapy (TAT) holds tremendous promise for treating cancer, as it offers the potential of delivering a highly cytotoxic dose to targeted cells while avoiding damage to the surrounding healthy tissue. TAT overcomes several barriers to traditional radiation therapy such as adaptive resistance and cell cycle progression. Currently a number of radionuclides that emit single alpha particles are under investigation, including the halogen ²¹¹At and the metallic isotopes ²¹³Bi, and ²¹²Pb. A growing subset of medical isotopes in this field includes the α-generator radionuclides ²²⁵Ac, ²²³Ra, ²²⁷Th, and ²³⁰U; isotopes that emit multiple α particles in their decay chains, dramatically increasing the potential delivered dose. To create a targeted alpha therapeutic comprising one of these radiometals, one must assemble 3 parts: a targeting moiety, a chelating ligand, and an appropriate radionuclide. Ideal properties of targeting constructs include facile internalization into, and retention of the decay products within, the target cell to achieve full cytotoxic potential and reduce the loss of the daughters to non-target tissues, thereby mitigating systemic radiotoxic events. Despite promising therapeutic potential established in pre-clinical and clinical studies, such designs have been slow to emerge. Reasons for this protracted development are many, including limited supply of radioisotopes, insufficient understanding of their biodistribution and biodosimetry, poor retention of daughter products at the target site, as well as inadequate chelation, one of the major drawbacks. Our approach is to clearly delineate the biodistribution of bioconjugate therapeutics, resulting dosimetry, mechanisms of induced cellular toxicity, efficacy, and safety, with a focus on ²²⁵Ac. Ongoing efforts aimed at addressing current limitations of TAT agents will be discussed, with the perspective of a pressing need for the development of new targeted α-therapy strategies.

Disclosure of interest: Part of the discussed work was supported by the U.S. Department of Energy’s Isotope Program in the Office of Nuclear Physics at the Lawrence Berkeley National Laboratory under Contract DE-AC02-05CH11231.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

High-Resolution Alpha Camera Imaging as a Tool for Developing Targeted Alpha Therapy

Tom Bäck ¹

Targeted alpha therapy (TAT) attracts increased interest, particularly for treatment of metastatic cancer. Before its full clinical potential can be realized, however, many of the current gaps of knowledge must be overcome. The often missing information relates to the highly localized, and often very heterogeneous, alpha-particle radiation energy distribution. In many cases, treatment planning based on whole-organ dosimetry will fail to predict the therapeutic and toxicity outcome in treatments when alpha-particle emitters. The alpha camera imaging system was developed to provide high-resolution quantitative imaging of alpha particles in tissue. The key elements of this system have been previously published. Here, an updated overview of the alpha camera imaging platform and results from a wide range of collaborative and published studies will be provided. Distribution data will be presented from imaging of several alpha-emitters including Ra-223, Th-227, Bi-213 and At-211. Several different issues of TAT will be addressed. Examples of such issues include intra-tumoural and intra-renal distribution; PRIT vs RIT; uniform vs non-uniform uptake in normal organs; and bone marrow imaging. Illustrative examples will be presented of how alpha camera imaging can be used for small scale 3D-dosimetry using voxel dose-kernel computations. The capability of quantum detection and imaging, ie. single-event imaging of individual alpha particles will also be shown. Importantly, preliminary imaging results will be presented for the first two patients of an ongoing bone biopsy study on patients being treated with Ra-223 chloride for treatment of castration resistant metastatic prostate cancer. The concept of mean absorbed dose to whole organs will therefore in many cases be misleading when evaluating, for example, dose-response relationships. Instead, the dosimetry from alpha-particle irradiation must be derived for the small-scale (sub-organ) level. This can be achieved using small-scale imaging of alpha-particle decay and dosimetric modelling.

References

1.Bäck T, Jacobsson L. The alpha-camera: A quantitative digital autoradiography technique using a charge-coupled device for ex vivo high-resolution bioimaging of alpha-particles. J Nucl Med. 2010;51:1616–23. doi: 10.2967/jnumed.110.077578. [DOI] [PubMed] [Google Scholar]
2.Chouin N, Lindegren S, Frost SH, Jensen H, Albertsson P, Hultborn R, et al. Ex vivo activity quantification in micrometastases at the cellular scale using the α-camera technique. J Nucl Med. 2013;54:1347–53. doi: 10.2967/jnumed.112.113001. [DOI] [PubMed] [Google Scholar]
3.Sgouros G, et al. MIRD monograph: radiobiology and dosimetry for radiopharmaceutical therapy with alpha-particle emitters. 2015 doi: 10.1053/j.semnuclmed.2019.11.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Chouin N, Lindegren S, Jensen H, Albertsson P, Bäck T. Quantification of activity by alpha-camera imaging and small-scale dosimetry within ovarian carcinoma micrometastases treated with targeted alpha therapy. Q J Nucl Med Mol Imaging. 2012;56:487–95. [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Production of Medical Radionuclides Using High Energy Accelerators

Cathy Cutler ¹

In 1931 Ernest Lawrence invented the cyclotron and with it the ability to produce radioactive isotopes of interest for biological applications. Since that time major advances have enabled the production of small compact cyclotrons to be installed at hospitals and pharmacies supporting the supply of short-lived radionuclides around the world. In the 1970’s and 80’s major accelerator facilities operating at 100 MeV and higher were installed in many of the national labs and used for production of radionuclides at much higher energy values than can be achieved on the small compact machines. These high energy accelerators play a critical role in supplying radionuclides such as Sr-82 used in Sr-82/Rb-82 generators for cardiac imaging. They continue to be upgraded to further production yields by installing beam rastering systems that have allowed higher intensities and thus higher production yields. Demand for isotopes that can be produced by these systems have also increased. The Linac proton energy at BNL can be incrementally tuned from 66 to 200 MeV in steps at 90, 118, 140, 160, 180 MeV. More than 90% of the pulses are directed via beamline to Brookhaven Linac Isotope Producer (BLIP). The beam can deliver both rastered and focused beam patterns at an average current as high as 165 µA. The beam is delivered to the BLIP and used for isotope production 7-8 months per year. Linear accelerators such as the one at Brookhaven National Laboratory when operating at maximum proton energy of 200 MeV can have simultaneous production of several medically relevant isotopes. Among those are Ac-225 (T_1/2=10.0 d), Se-72/As-72 (T_1/2=26 h), Sr-82/Rb-82 (T_1/2=1.26 min) and Ti-44/Sc-44 (T_1/2=3.97 h). Production of these novel radionuclides and recent enhancements will be presented.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Moving Radiopharmaceuticals from the Lab to The Patient in Europe

Clemens Decristoforo ¹

Scientists are bringing an ever greater number of novel radiopharmaceuticals towards the point of clinical translation. New insights in neurosciences, novel targets in oncology, the popular concept of theranostics and the availability of new radionuclides are great stimuli for the translation. This presentation will provide an overview on the process of moving radiopharmaceuticals from the lab to the patient in Europe, but also address the challenges we face today in this process. Radiopharmaceuticals in Europe are drugs, defined as medicinal products in legislation. Therefore, clinical trials have to follow regulations regarding Investigational Medicinal Products (IMPs). European legislation has changed with the implementation of the New Clinical Trial regulation EU No 536/2014.[1] This regulation will be fully implemented in 2019 and takes some specifics of radiopharmaceuticals into considerations.[2] The way of submission of trials will change and harmonized within the EU, facilitation multinational approaches,[3] these changes will be described and explained. A number of regulatory aspects of radiopharmaceuticals already have to be taken into account in the development of a new compound. These can be divided in “quality aspects” related to chemistry and formulation, and “safety aspects” related to pharmacology and toxicology. With respect the quality of a new radiopharmaceutical one of the greatest challenge is the compliance with Good Manufacturing Practices (GMP). This already starts with the radionuclide, the way of synthesis (automated or manually) but also aspects related to quality of starting materials and facilities, which will be discussed. For the submission of a clinical trial the information of the IMP has to be compiled in a so called Investigational Medicinal Product dossier, which will be explained in this presentation. In relation of the preclinical safety evaluation of a new radiopharmaceutical one challenge lies within toxicity testing of the cold compounds, where the European Medicines agency has initiated new guidance. Other requirements related to pharmacokinetics and pharmacology will be exemplified including in vitro and in vivo data to be generated before human application can be envisaged. Overall this talk will give an insight in Europe specific aspects and the regulatory challenges related to radiopharmacy and try to help to untangle the web of regulations.[4]

References

1. [Last accessed on 2018]. Available from: http://www.ec.europa.eu/health/human-use/clinical-trials/regulation_en .
2.Decristoforo C, Penuelas I, Elsinga P, Ballinger J, Winhorst AD, Verbruggen A, et al. Radiopharmaceuticals are special, but is this recognized?The possible impact of the new clinical trials regulation on the preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging. 2014;41:2005–7. doi: 10.1007/s00259-014-2838-z. [DOI] [PubMed] [Google Scholar]
3.Decristoforo C, Penuelas I, Patt M, Todde S. European regulations for the introduction of novel radiopharmaceuticals in the clinical setting. Q J Nucl Med Mol Imaging. 2017;61:135–44. doi: 10.23736/S1824-4785.17.02965-X. [DOI] [PubMed] [Google Scholar]
4.Lange R, ter Heine R, Decristoforo C, Peñuelas I, Elsinga PH, van der Westerlaken MM, et al. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: A concise overview and practical guidance for a risk-based approach. Nucl Med Commun. 2015;36:414–22. doi: 10.1097/MNM.0000000000000276. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Coordination Chemistry of Zirconium Radiopharmaceuticals

Paul Donnelly ¹

Antibodies labelled with positron-emitting radioactive isotopes can be used as tracers for positron emission tomography (PET) imaging and are of interest as companion diagnostics to therapeutic antibodies to allow selection of patients who will best respond to antibody therapy. Zirconium-89 is a positron-emitting isotope with a relatively low translational energy (395.5 keV) and a half-life of 3.3 days that is well suited to antibody-based PET imaging.[1] One approach to incorporate ⁸⁹Zr into antibodies is to attach a ligand to the anibody that binds to ⁸⁹Zr(IV) with high affinity. The bacterial siderophore desferrioxamine B (H₃DFO) is a reasonable ligand for ⁸⁹Zr(IV) radiopharmaceuticals and has been used in human clinical studies but is only a hexadenatate ligand.[2] It is possible that octadentate ligands may enable the synthesis of 8-coordinate ⁸⁹Zr complexes with improved in vivo stability.[3] A review of the important aspects of the coordination chemistry of Zr(IV) will be presented highlighting important aspects for the use of the isotope in immunoPET as well as a new ligand capable of forming stable complexes with ⁸⁹Zr(IV). A squaramide ester derivative of desferrioxamine B (H₃DFO) that is compatible with aqueous solvents was syntheised to attach the siderophore to the antibody trastuzumab. The new conjugates were radiolabelled with ⁸⁹Zr(IV) and ⁸⁹ZrDFOSq-trastuzumab was administered via tail-vein injection to both human ovarian high-copy HER2 and SKOV3 xenograft models. Small animal PET imaging was performed at 24 to 96 h post administration for each study. ⁸⁹ZrDFOSq-trastuzumab was also administered to xenograft-bearing mice with the HER2 high-copy breast cell line BT474. In all cases ⁸⁹ZrDFOSq-trastuzumab resulted in high quality PET images. A squaramide ester derivative of desferrioxamine B, H₃DFOSqOEt can be used for efficient bioconjugation reactions to antibodies, and proteins and subsequent radiolabeling with ⁸⁹Zr(IV). Zirconium-89 complexes of H₃DFOSq are more stable than thiourea containing analogues possibly due to the ligand forming 8-coordinate complexes. The conjugates with trastuzumab were radiolabeled with ⁸⁹Zr(IV) and the new constructs were used to obtain high quality PET images in three models of HER2 positive tumours.[4]

References

1.Dijkers EC, Kosterink JG, Rademaker AP, Perk LR, van Dongen GA, Bart J, et al. Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging. J Nucl Med. 2009;50:974–81. doi: 10.2967/jnumed.108.060392. [DOI] [PubMed] [Google Scholar]
2.Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87:586–92. doi: 10.1038/clpt.2010.12. [DOI] [PubMed] [Google Scholar]
3.Patra M, Bauman A, Mari C, Fischer CA, Blacque O, Häussinger D, et al. An octadentate bifunctional chelating agent for the development of stable zirconium-89 based molecular imaging probes. Chem Commun (Camb) 2014;50:11523–5. doi: 10.1039/c4cc05558f. [DOI] [PubMed] [Google Scholar]
4.Rudd SE, Roselt P, Cullinane C, Hicks RJ, Donnelly PS. A desferrioxamine B squaramide ester for the incorporation of zirconium-89 into antibodies. Chem Commun (Camb) 2016;52:11889–92. doi: 10.1039/c6cc05961a. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Geant4: a Monte Carlo Code for Dosimetry of Radiopharmaceuticals

Susanna Guatelli ¹

Geant4 is a widely used Monte Carlo (MC) code, born for High Energy Physics experiments, and then extended to space science and medical physics applications.[1] Geant4 is developed and maintained by an international Collaboration (more than 100 members), is open-source and free. Platforms such as GATE (http://www.opengatecollaboration.org/), GAMOS (http://fismed.ciemat.es/GAMOS/) and TOPAS (http://www.topasmc.org/) allow an easy use of Geant4 in the medical physics community. Geant4 has ad-hoc physics extensions to describe the interactions of particles with biological targets, down to the eV scale. It can be used to investigate the effect of radiation emitted by radiopharmaceuticals at macroscopic level (mm size), cellular and DNA scales. Geant4 has also advanced capability in modelling geometries, from analytical human phantom models (e.g. Geant4 advanced example human_phantom) and voxelised geometries imported from DICOM files (e.g. Geant4 extended example DICOM_interface) to the modelling of the DNA helix. The functionality of Geant4 for dosimetry of radiopharmaceuticals will be illustrated together with an example of its application in Targeted Alpha Therapy. Geant4 is a mature Monte Carlo code which is well suited to investigate the effect of radiation emitted by radiopharmaceuticals in organs, at mm scale as well as micro and nano scales.

Reference

1.Agostinelli S, et al. Geant4 collaboration. Geant4: A simulation Toolkit. NIM A. 2003:250–303. [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

New Approaches in Carbon-11 Chemistry

Christer Halldin ¹

PET provides a new way to image the function of a target and by elevating the mass, to pharmacologically modify the function of the target. The main applications of radioligands in brain research concern human neuropsychopharmacology and the discovery and development of novel drugs to be used in the therapy of psychiatric and neurological disorders. A basic problem in PET brain receptor studies is the lack of useful radioligands with ideal binding characteristics. During the past decade more than hundred neurotransmitters have been identified in the human brain. Most of the currently used drugs for the treatment of psychiatric and neurological disorders interact with central neurotransmission. Several receptor subtypes, transmitter carriers, and enzymes have proven to be useful targets for drug treatment. Molecular biological techniques have now revealed the existence of hundreds of novel targets for which little or no prior pharmacological or functional data existed. Due to the lack of data on the functional significance of these sites, pharmacologists are now challenged to find the physiological roles of these receptors and identify selective agents and possible therapeutic indications. During the past decade various ¹¹C- and ¹⁸F-labeled PET radioligands have been developed for labeling some of the major central neuroreceptor systems. There is still a need to develop pure selective PET radioligands for all the targets of the human brain. This presentation will cover the more recent and promising developments of ¹¹C-labeling radiochemistry and its utility in the production of novel radiopharmaceuticals, with special emphasis to labeling methods that have the greatest potential to be translated into clinical PET imaging. It will also compare the advantages and disadvantages with the use of either ¹¹C- and ¹⁸F-labeled PET radioligands. The need for novel PET radioligands for clinical PET imaging is increasing and ¹¹C-radioligands are especially important within clinical research and drug development.

References

1.Dahl K, Halldin C, Schou M. New methodologies for the preparation of carbon-11 labeled radiopharmaceuticals. Clin Transl Imaging. 2017;5:275–89. doi: 10.1007/s40336-017-0223-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Radiometal Chemistry: The Chemistry Behind Emerging Radiometals for Theranostics

Petr Hermann ¹

A theranostic pair of radioisotopes (a combination of PET/SPECT and therapeutic radioisotopes) enables diagnosis and therapy with the same chemical entity. To be used in medicine, the metal radioisotopes must be bound by suitable (bifunctional) chelators to form complexes which have to be stable in-vivo. The chelators have to match properties required by the metal ion, e.g. a kind of donor atoms, coordination number, stereochemistry etc. It is more important for radiotherapeutics due to their high toxicity in non-target tissue than for imaging agents. Theranostic pair is commonly considered to be composed of the radioisotopes of the same metal element as imaging and therapeutic agents are naturally the same. However, there is also possible to consider a theranostic “pair” composed from two different metal ions. Such combination might be even more convenient as mainly the radioisotope half-lives could be much easily matched. It could be accomplished through a combination of two different chelators, each selectively binding just one metal ion of the pair, into one molecule. Besides “traditional” pairs as 86/90-Y, there is still worth to consider combination 61/64/67-Cu, and other ones are becoming to be more popular, e.g. 43/44/47-Sc or some transition metals. Short-lived therapeutic alpha-emitters can be combined with 68-Ga. For each metal radioisotope or their combination, the most suitable chelators can be designed. The theranostic pairs of radiometals will serve best if the metals will be bound in chelators which are designed especially for them, and which will ensure fast and efficient labelling (the chelator selectivity is important) as well as in-vivo stability (kinetic inertness is often crucial). These parameters are even more important if two chelators of different structure and properties are combined together in “two-metal” theranostics.

References

1.Notni J, Hermann P, Dregely I, Wester HJ. Convenient synthesis of (68)Ga-labeled gadolinium(III) complexes: Towards bimodal responsive probes for functional imaging with PET/MRI. Chemistry. 2013;19:12602–6. doi: 10.1002/chem.201302751. [DOI] [PubMed] [Google Scholar]
2.Pniok M, Kubíček V, Havlíčková J, Kotek J, Sabatie-Gogová A, Plutnar J, et al. Thermodynamic and kinetic study of scandium(III) complexes of DTPA and DOTA: A step toward scandium radiopharmaceuticals. Chemistry. 2014;20:7944–55. doi: 10.1002/chem.201402041. [DOI] [PubMed] [Google Scholar]
3.Nagy G, Szikra D, Trencsányi G, et al. AAZTA: An ideal chelating agent for the development of 44Sc PET imaging agents. Angew Chem Int Ed Engl. 2017;56:2118–22. doi: 10.1002/anie.201611207. [DOI] [PubMed] [Google Scholar]
4.Wurzer A, Seidl C, Morgenstern A, Bruchertseifer F, Schwaiger M, Wester HJ, et al. Dual-nuclide radiopharmaceuticals for positron emission tomography based dosimetry in radiotherapy. Chemistry. 2018;24:547–50. doi: 10.1002/chem.201702335. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Moving from the Lab to the Patient in the USA

Jason Lewis ¹

This talk is designed to present the audience with the general approach for translating new imaging agents to the clinic in the USA. The methods and regulatory hurdles to do this will be discussed.

Learning objectives:

Learn about the path for translation of new imaging agents from the bench to the clinic
Learn about examples of recent agents that have been translated in the oncology setting.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

New Chelators Enable One-Step Kit-Based Radiosynthesis of Receptor-Targeted Gallium-68 Radiopharmaceuticals

Michelle Ma ¹

A pharmaceutical-grade ⁶⁸Ga generator has recently become commercially available, providing hospitals with on-site access to a GMP-grade diagnostic PET radionuclide without the need for local cyclotron facilities. The most widely used ⁶⁸Ga radiopharmaceuticals consist of ⁶⁸Ga coordinated to a chelator that is attached to a peptide for targeting cell-surface receptors of tumours: many centres routinely produce diagnostic ⁶⁸Ga-HBED-PSMA and ⁶⁸Ga-DOTA-TATE for whole-body PET imaging of prostate and neuroendocrine cancers respectively. These radiotracers have had significant impact on patient management in centres where they are available, but the complexity of their radiosynthesis in hospitals is a barrier to widespread implementation. Recently, several chelators have been evaluated and/or developed for ⁶⁸Ga radiolabelling of peptides under ambient conditions. These include chelators based on 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups, 6-amino-1,4-diazepanes with acetate substituents (DATA), a siderophore-derived macrocyclic chelator with hydroxamate groups (FSC), the acyclic siderophore desferrioxamine-B (which also contains hydroxamates), an acyclic chelator based on a substituted pyridine carboxylate with an N₄O₂ binding mode (DEDPA) and tris (hydroxypyridinone) (THP) derivatives based on 1,6-dimethyl-3-hydroxypyridin-4-one units. These chelators quantitatively coordinate ⁶⁸Ga³⁺ at near-neutral pH, room temperature and low concentrations of chelator-peptide bioconjugate. Such chelators will enable one-step, kit-based radiosyntheses of ⁶⁸Ga-radiopharmaceuticals. Kit-based ⁶⁸Ga-radiopharmaceuticals will greatly increase ⁶⁸Ga PET access to hospitals that routinely prepare ^99mTc kit-based radiopharmaceuticals, but lack expertise or facilities to implement complicated automated synthetic technologies. This chelator technology will expand the use of the ⁶⁸Ga generator for the benefit of more hospitals and patients.

Reference

1.Tsionou MI, Knapp CE, Foley CA, Munteanu CR, Cakebread A, Imberti C, et al. Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling. RSC Adv. 2017;7:49586–99. doi: 10.1039/c7ra09076e. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Radiometal Production: In Reactors

Renata Mikolajczak ¹

Nuclear reactors are the source of neutrons of various energies which can be utilized for irradiation of radiometals in nuclear reactions with elements of target material. There are a number of radiometals which can be produced in nuclear reactors, with ¹⁵³Sm, ¹⁷⁷Lu and ¹⁶⁶Ho on top of the list. There is also a need for other ones, with various chemical and physical characteristics, such as ⁴⁷Sc, ⁶⁷Cu etc. The characteristics of neutron flux, a parameter specific for each individual reactor, and the composition of the target material will determine the final specific activity of the desired radionuclide. Special attention is given to radiometals which can be obtained in carrier-free form from (n,p) and (n,γ) reactions giving a parent radionuclide decaying in short time to required daughter radioisotope. The processing of such targets requires separation chemistry. The ultimate goal is to obtain the radiometal with high specific activity, radionuclide and chemical purity, in the solution suitable for radiolabeling of various molecules for medicinal use. From the pharmaceutical perspective the radiometal in solution for radiolabelling can be granted a status of medicinal product as a precursor of radiopharmaceutical.

Reference

1.Parus JL, Mikolajczak R. Beta-emitting radionuclides for peptide receptor radionuclide therapy. Curr Top Med Chem. 2012;12:2686–93. doi: 10.2174/1568026611212230006. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Organotrifluoroborates as Prosthetic Groups for Single-Step F18-Labeling of Molecularly Complex Molecules

David Perrin ¹

Growth in the oncology tracer market is driven by peptides and other molecules that detect specific molecular targets whose presence leads to cancer. While several PET-useful isotopes exist, ¹⁸F-fluoride has a track-record of FDA clearance, is produced at Curie-levels. Its excellent nuclear capabilities including a moderate half-life, low positron emission energy, and isotopic purity make it a choice isotope for PET. Nevertheless, the challenges for ¹⁸F-labeling large molecules are considerable; these include a short half-life and typically, the need to work in anhydrous conditions and at high temperature. In seeking an aqueous reaction along with kit-like simplicity, we have developed organoborates that can be pre-conjugated to peptides to provide precursors that are ¹⁸F-labeled in a single aqueous step. To streamline labeling, we have explored isotope exchange (IEX), the advantage being that the unlabeled ¹⁹F-precursor and ¹⁸F-labeled product are chemically identical. Peptides including octreotate, bombesin, rhodamine-dimeric-RGD, bradykinin, LLP2A, MSH, and diamino-acid ureas for targeting PSMA have been synthesized by standard methods. With a pendant azide or alkyne, these peptides are “click” conjugated to organotrifluoroborates. NCA [¹⁸F]fluoride ion (~1Ci) is trapped on a small QMA cartridge and eluted directly into a tube containing the peptide-BF₃. Following a 20 min IEX, the peptide is applied to a sep-pak to remove free fluoride whereupon the ¹⁸F-labeled peptide-BF₃ is eluted into 50% EtOH and used for imaging studies. Labeling proceeds with operational simplicity in a fully shielded hot-cell with radiochemical yields of 10-30% at molar activities of 2-5 Ci/µmol within 25 min. Uptake values range from 5-20% ID/g with some tumour contrast ratios (T: Blood, T: Muscle) in excess of 100. Organotrifluoroborates as radioprosthetics are labeled in water in a single step and provide a robust and perhaps generalizable means to generate ¹⁸F-labeled radiotracers.

References

1.Liu Z, Pourghiasian M, Bénard F, Pan J, Lin KS, Perrin DM, et al. Preclinical evaluation of a high-affinity 18F-trifluoroborate octreotate derivative for somatostatin receptor imaging. J Nucl Med. 2014;55:1499–505. doi: 10.2967/jnumed.114.137836. [DOI] [PubMed] [Google Scholar]
2.Liu, et al. A broadly applicable one-step method for 18F-labelling. Angewandte Chem. 2014;53:11876–80. doi: 10.1002/anie.201406258. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Production of Medical Isotopes with Electron Linacs

David Rotsch ¹

The use of electron linacs for the production of radioisotopes has not been experimentally explored to any tangible depth because sources of photons with sufficient energy and flux for production have only recently become available. High specific activity (SA) isotopes can be routinely achieved through (γ,p) reactions. The photonuclear production and chemical purification of ⁴⁷Sc and ⁶⁷Cu from ^natTi and enriched ⁶⁸Zn targets, respectively, will be discussed. Targets were irradiated with Argonne’s 55 MeV/30 kW e-linac. The targets were mounted in target stations at the end of a beam lines with a water-cooled Be-exit window. Incident electrons were converted to photons with water-cooled tungsten or tantalum convertors. Scandium-47 was produced from pressed pellets of ^natTiO₂ and ^natTiC. The target material was dissolved and ⁴⁷Sc was isolated and purified by column chromatography. Copper-67 was produced from enriched ⁶⁸Zn cast as large cylinders (~100 g). Copper-67 was isolated from the target material via sublimation of the target material. Copper-67 was then dissolved and then purified by column chromatography. Radioscandiums (^46-48Sc) were isolated from TiO₂ dissolved in H₂SO₄ using an Eichrom DGA normal chromatographic resin. All radioscandiums were eluted form the column with HCl (0.1 M) in >90% recovery with SA of 888.0 GBq/mg (⁴⁷Sc/Sc, EOB).[1] Copper-67 was isolated from ⁶⁸Zn by sublimation of the target material under vacuum at 650^oC. Copper-67 was dissolved in HCl (8 M) and concentrated HNO₃ and then purified with a Dowex AG1X8 anion exchange resin. Copper-67 was isolated in HCl (0.1 M) in >90% recovery with SA of 843.6 GBq/mg (⁶⁷Cu/Cu, EOB). Electron linacs are becoming more prevalent and represent untapped sources for isotopes. The relatively low production rates of (γ,p) reactions can be overcome with increased power (current) of the incident beam. Here the production of high SA ⁴⁷Sc and ⁶⁷Cu has been demonstrated.

1. Disclosure of interest: Argonne National Laboratory’s work was supported under U.S. Department of Energy contract DE-AC02-06CH11357. U.S. DOE Office of Nuclear Physics Isotope Program. Argonne national Laboratory is operated for the U.S. Department of Energy by U Chicago Argonne, LLC.

Reference

1.Rotsch DA, Brown MA, Nolen JA, Brossard T, Henning WF, Chemerisov SD, et al. Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets. Appl Radiat Isot. 2018;131:77–82. doi: 10.1016/j.apradiso.2017.11.007. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

New Approaches to Late-Stage Radiolabeling of Bioactive Molecules

Peter Scott ¹

The development of novel PET radiopharmaceuticals is critically dependent on the availability of methods to incorporate the desired radioisotope into a scaffold of interest. In recent years, there has been significant advancement in methods for the late-stage radiolabeling of bioactive molecules and drug scaffolds with fluorine-18. Metal-mediated reactions with [¹⁸F]fluoride are an example of one such advancement which, in a relatively short period of time, have changed the way radiochemists form C-¹⁸F bonds and revolutionized the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging (or impossible) to synthesize using traditional fluorine-18 radiochemistry. This presentation will cover our recent progress developing new metal-mediated approaches to late-stage fluorination using high specific activity nucleophilic [¹⁸F]fluoride.[1,2,3,4] [¹⁸F]Fluoride was produced in a PETTrace cyclotron using the ¹⁸O(p, α) ¹⁸F nuclear reaction, trapped on a QMA cartridge and eluted to produce aq.[¹⁸F]KF or [¹⁸F]AgF. The salt solutions were azeotropically dried and then redissolved. These stock solutions were then used to carry out test reactions with various precursors (ArX, where X = IMes, BX₂, SnR₃ or H). Reactions were analyzed by radio-TLC and HPLC to determine yields. Numerous fluorine-18 labeled arenes have been synthesized from the corresponding ArX precursors (where X = IMes, BX₂, SnR₃ or H). All of the methods are tolerant of electron-deficient, -neutral or -rich arenes. The reactions have been fully automated on radiochemistry synthesis modules, and the high yields and mild conditions make the methods well-suited for the synthesis of clinical radiotracers and radiolabeling of drug-like molecules. Transition-metal-mediated reactions that convert C–I, C–B, C–Sn and C-H bonds into C–¹⁸F bonds using high specific activity nucleophilic [¹⁸F]fluoride have been developed that allow facile radiolabeling of a range of arenes and are enabling the synthesis and evaluation of many new radiotracers for PET imaging.

References

1.Ichiishi N, Brooks AF, Topczewski JJ, Rodnick ME, Sanford MS, Scott PJ, et al. Copper-catalyzed [18F]fluorination of (mesityl)(aryl)iodonium salts. Org Lett. 2014;16:3224–7. doi: 10.1021/ol501243g. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Mossine AV, Brooks AF, Makaravage KJ, Miller JM, Ichiishi N, Sanford MS, et al. Synthesis of [18F]Arenes via the copper-mediated [18F]Fluorination of boronic acids. Org Lett. 2015;17:5780–3. doi: 10.1021/acs.orglett.5b02875. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Makaravage KJ, Brooks AF, Mossine AF, et al. Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF. Org Lett. 2016;18:5440. doi: 10.1021/acs.orglett.6b02911. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.McCammant MS, Thompson S, Brooks AF, Krska SW, Scott PJH, Sanford MS, et al. Cu-mediated C-H 18F-fluorination of electron-rich (Hetero)arenes. Org Lett. 2017;19:3939–42. doi: 10.1021/acs.orglett.7b01902. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Targeted Alpha Particle Radiotherapy: Prospects and Problems

Michael Zalutsky ¹

Radionuclides that decay by the emission of α-particles offer the exciting prospect of combining cell-specific molecular targets with radiation having a tissue range of only a few cell diameters. However, a potential problem resultant from this short range is the effect of heterogeneities in dose deposition on therapeutic efficacy. Alpha particles are radiation of high linear energy transfer, offering important radiobiological advantages for cancer therapy including a therapeutic effect that is nearly independent of dose rate, presence of oxygen, and cell cycle status. The properties of alpha-emitters are best suited for the treatment of compartmentally spread neoplasms such as ovarian carcinoma and neoplastic meningitis, as well as tumours of the circulation such as lymphoma and leukaemia. In addition, targeted anti-vascular radiotherapy is a particularly attractive application of alpha emitters because of the possibility of achieving more efficient cell kill than might be possible with strategies requiring direct binding of the labelled compound to the tumour cells themselves. Alpha emitting radionuclides that have now been evaluated in patients include 46-min ²¹³Bi, 7.2-h ²¹¹At, 11-day ²²³Ra, and 10-day ²²⁵Ac. Radiochemical strategies for labelling a variety of biomolecules with these and other alpha emitters are available. One of the biggest challenges facing the development of alpha-particle targeted radiotherapy is the availability of sufficient radionuclide to perform clinical investigations. in addition, with longer lived radionuclides decaying by the emission of multiple shorter lived alpha emitting daughters, minimizing deleterious effects to normal tissues after their escape must be considered. From a radiochemistry perspective, other important aspects are the development of scaled up radiolabelling procedures that are adaptable to GMP conditions and methodologies that are not compromised by radiolysis. In summary, although the results of most clinical trials performed to date indicate that targeted alpha-particle therapy is a promising strategy for cancer treatment, practical problems must be overcome before this approach has a meaningful clinical impact.

References

1.McDevitt MR, Sgouros G, Sofou S. Targeted and nontargeted α-particle therapies. Ann Rev Biomed Eng. 2018 doi: 10.1146/annurev-bioeng-062117-120931. doi: 10.1146/annurev-bioeng-062117-120931. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Renal: New Technologies and Applications in Nuclear Medicine: Current Applications in Renal Scintigraphy and Glomerular Filtration Rate Evaluation

Bridget Chappell ¹

Nuclear Medicine imaging and in vitro laboratory procedures provide important diagnostic information in the evaluation of the genitourinary system. Technetium-99m (^99mTc) and Chromium-51 (⁵¹Cr) based radiopharmaceutical imaging procedures and associated in vitro assay and calculations of the Glomerular Filtration Rates (GFR) are widely accepted methodologies in assessing the renal function of patients with diabetes, post chemotherapy and potential donors. The presentation will present an overview of the current practices in radionuclide renal imaging procedures. The presentation will describe the clinical indications, radiopharmaceuticals used, imaging techniques and technical aspects of the common nuclear medicine renal imaging procedures in practice. Laboratory quantitative applications will also be reviewed including procedure indications, analysis techniques and a comparison/merits of different types of radiopharmaceuticals used for quantitation of GFR. Renal scintigraphy and GFR estimations of renal function are common practices in a Nuclear Medicine Department. Technologists are required to be well versed in and be able follow a standardised practice, to ensure consistency and accuracy of results, which are often crucial in the clinical management of the patient.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Glomerular Filtration Rate Measurement in the Era of Peptide Receptor Radiation Therapy Therapy

Belkis Erbas ¹

Theranostics have gained an increasing clinical application for the therapy of various cancers. Peptide receptor radionuclide therapy is highly efficient for the metastatic or inoperable neuroendocrine tumours, however kidneys have been considered the “critical organ” because of the renal absorbed radiation dose. Severe renal toxicity, classified as grade 4-5 was reported ranging from 1% to 14% in the literature. Routinely, serum creatinine or GFR estimation based on creatinine has been used as a measure of renal function in the monitoring of renal toxicity. Most commonly used formulas for estimation of GFR are “Modifications of Diet in Renal Disease” (MDRD) equation and “Cockcroft-Gault” formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function. Radionuclide methods provide more accurate measure of renal function in patients receiving theranostics, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51- ethylenediaminetetraacetic acid (EDTA), or measurement of Tc-99m-MAG3 clearance, particularly in patients with preexisting risk factors for long-term nephrotoxicity. In this lecture, renal function measurement techniques and renal toxicity due to theranostics will be discussed.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Complementary Role of Renal Nuclear Medicine in Oncology

Belkis Erbas ¹

Oncologic pathologies might affect the kidney directly or indirectly. Primary tumours of kidney, invasion of cortical tissue by metastatic tumour, or obstruction of collecting system and bladder by the mass effect of intraabdominal/pelvic tumour may result in the impairment of renal function. Radiation nephropathy due to renal irradiation is an important complication of external beam radiation therapy or internal radiation therapy such as peptide receptor radiation therapy. Nephrotoxic chemotherapy is another cause of nephrotoxicity and renal function impairment. Glomerular filtration and tubular secretion are the major elimination pathways for antineoplastic agents and their metabolites. Intravascular volume depletion, concomitant use of other drugs (aminoglycoside antibiotics, nonsteroidal anti-inflammatory drugs) and contrast material may have further contribution to the renal functional impairment. When acute or chronic nephrotoxicity occurs, laboratory findings may vary from asymptomatic slight creatinine rise to acute renal injury and renal failure. Routinely, serum creatinine or cystatin C levels are used for the monitoring. GFR estimation formulas based on plasma creatinine values are also used for the GFR estimation, however, they are not sufficiently accurate methods for renal function measurements. Radionuclide methods, based on the plasma or urinary clearance of radiotracers, such as ⁵¹Cr-EDTA, ^99mTc-DTPA using single or multi-sample methods with or without urinary sampling, provide more reliable results. Renal scintigraphy using glomerular or tubular radiopharmaceuticals are used for the imaging and calculating the renal function/differential renal function, evaluation of the presence and level of obstruction, and follow-up the function. PET imaging with¹⁸F-FDG is helpful for the staging of genitourinary tumours, as well as, for the monitoring of therapy response or recurrence detection. Recently, Ga-68 labelled EDTA has been used for the dynamic PET imaging of renography and GFR measurement. Another application of renal imaging is the measurement of individual kidney uptake of Y-90 or Lu-177 labeled somatostatin analogs and prediction of renal absorbed dose in order to minimize the renal toxicity.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Guidelines for GFR Measurement: What to do, When to do it, and Where the Errors Occur

Andrew Hilson ¹

The presentation is based on the draft BNMS GFR guidelines.

How many samples?

-ISCORN/Radionuclides in Nephrology group recommended single sample if GFR > 30 ml/min.[1] Recommended Christensen-Groth method[2]

-BNMS (2004) recommended 3-sample method because of QC issues, but now recommend single-sample approach:

-Use Fleming method if GFR > 25 ml/min with same-day sampling.[3]

-Use Gref and Karp method if GFR<25 ml/min with 24h sample.[4]

-If significant third space use 4-sample method of Wickham et al.[4]

Agent?

^99mTc-DTPA or ⁵¹Cr-EDTA.

QC?

There are no reliable intrinsic QC methods-rely on good technique.[5]

References

1.Blaufox MD, Aurell M, Bubeck B, Fommei E, Piepsz A, Russell C, et al. Report of the radionuclides in nephrourology committee on renal clearance. J Nucl Med. 1996;37:1883–90. [PubMed] [Google Scholar]
2.Christensen AB, Groth S. Determination of 99mTc-DTPA clearance by a single plasma sample method. Clin Physiol. 1986;6:579–88. doi: 10.1111/j.1475-097x.1986.tb00790.x. [DOI] [PubMed] [Google Scholar]
3.Fleming JS, Persaud L, Zivanovic MA. A general equation for estimating glomerular filtration rate from a single plasma sample. Nucl Med Commun. 2005;26:743–8. doi: 10.1097/01.mnm.0000171783.18650.80. [DOI] [PubMed] [Google Scholar]
4.Wickham F, Burniston MT, McMeekin H, Hilson AJ, Burroughs AK. Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease. Nucl Med Commun. 2015;36:168–79. doi: 10.1097/MNM.0000000000000235. [DOI] [PubMed] [Google Scholar]
5.Gref MC, Karp KH. Single-sample 99mTc-diethylenetriamine penta-acetate plasma clearance in advanced renal failure by the mean sojourn time approach. Nucl Med Commun. 2009;30:202–5. doi: 10.1097/MNM.0b013e328315e0c6. [DOI] [PubMed] [Google Scholar]
6.McMeekin H, Wickham F, Barnfield M, Burniston M. Effectiveness of quality control methods for glomerular filtration rate calculation. Nucl Med Commun. 2016;37:756–66. doi: 10.1097/MNM.0000000000000520. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Captopril Renography in the 21^st Century

Andrew Hilson ¹

The role of captopril renography in renovascular disease (RVD) was first shown by Wenting in1984 who showed that captopril reduced function in a kidney with RVD.[1] This was followed by the development of the single-dose captopril study,[2] which showed that using simple clinical criteria it was possible to select a population which showed significant RVD in about 33%. The technique was taken further in the European Multicentre Study,[3] which showed that the technique was very good at selecting patients who would or would not benefit from revascularistion. In 1996 there was a consensus guideline.[4] In 2009, the ASTRAL study[5] showed no benefit from revascularisation in patients with RVH, and this was confirmed in the 2015 CORAL study. So, what is the role of captopril renography? Both ASTRAL and CORAL only enrolled patients in whom there was equipoise as to the possible benefit of revascularisation. Captopril renography is of use in confirming or excluding the need for revascularisation - selecting which patients should have intervention, and which can be treated medically.

References

1.Wenting GJ, Tan-Tjiong HL, Derkx FH, de Bruyn JH, Man in't Veld AJ, Schalekamp MA, et al. Splint renal function after captopril in unilateral renal artery stenosis. Br Med J (Clin Res Ed) 1984;288:886–90. doi: 10.1136/bmj.288.6421.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Maher ER, Othman S, Frankel AH, Sweny P, Moorhead JF, Hilson AJ, et al. Captopril-enhanced 99mTc DTPA scintigraphy in the detection of renal-artery stenosis. Nephrol Dial Transplant. 1988;3:608–11. doi: 10.1093/oxfordjournals.ndt.a091714. [DOI] [PubMed] [Google Scholar]
3.Fommei E, Ghione S, Hilson AJ, Mezzasalma L, Oei HY, Piepsz A, et al. Captopril radionuclide test in renovascular hypertension: A European multicentre study. European multicentre study group. Eur J Nucl Med. 1993;20:617–23. doi: 10.1007/BF00176558. [DOI] [PubMed] [Google Scholar]
4.Taylor A, Nally J, Aurell M, Blaufox D, Dondi M, Dubovsky E, et al. Consensus report on ACE inhibitor renography for detecting renovascular hypertension. Radionuclides in nephrourology group. Consensus group on ACEI renography. J Nucl Med. 1996;37:1876–82. [PubMed] [Google Scholar]
5.ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, et al. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009;361:1953–62. doi: 10.1056/NEJMoa0905368. [DOI] [PubMed] [Google Scholar]
6.Herrmann SM, Saad A, Textor SC. Management of atherosclerotic renovascular disease after cardiovascular outcomes in renal atherosclerotic lesions (CORAL) Nephrol Dial Transplant. 2015;30:366–75. doi: 10.1093/ndt/gfu067. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Imaging in the Assessment of Urinary Tract Infection

Monica Rossleigh ¹

Urinary tract Infection (UTI) is a common problem. Despite this, the role of imaging in this clinical context remains controversial. The three imaging modalities utilised are ultrasound examination, micturating cystourethrography and DMSA renal cortical scintigraphy. A review of the literature will be presented and an evaluation of a variety of guidelines formulated by different august bodies for the assessment of this clinical problem will be undertaken. Individual centres will need to determine which of the different guidelines to follow that best suits the philosophy of management of this condition in their institution.

References

1.Edefonti A, Tel F, Testa S, De Palma D. Febrile urinary tract infections: Clinical and laboratory diagnosis, imaging, and prognosis. Semin Nucl Med. 2014;44:123–8. doi: 10.1053/j.semnuclmed.2013.10.004. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Read with the Experts Session - Diuretic Renography

Monica Rossleigh ¹, Anita Brink ¹, Zvi Bar Sever ¹, Meg Parisi ¹

With the increasing use of ultrasound assessment of the foetus during pregnancy, there has been a need to evaluate the antenatal diagnosis of hydronephrosis. Diuretic renography is being frquently applied to this condition and it has a significant role in the management of these patients. The interpretation of diuretic renography will be assessed by reviewing a number of cases presented by speakers from around the world. Utilizing a variety of cases to be presented with audience participation in their interpretation will result in an improvement in reporting of diuretic renography, including interpreting difficult and challenging cases. Clinical issues that impact on the interpretation of diuretic renograms will be outlined. At the completion of this session, participants in the audience will be able to interpret diuretic renography with greater confidence.

References

1.Gordon I, Piepsz A, Sixt R Auspices of Paediatric Committee of European Association of Nuclear Medicine. Guidelines for standard and diuretic renogram in children. Eur J Nucl Med Mol Imaging. 2011;38:1175–88. doi: 10.1007/s00259-011-1811-3. [DOI] [PubMed] [Google Scholar]
2.Shulkin BL, Mandell GA, Cooper JA, Leonard JC, Majd M, Parisi MT, et al. Procedure guideline for diuretic renography in children 3.0. J Nucl Med Technol. 2008;36:162–8. doi: 10.2967/jnmt.108.056622. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Technologist: New Applications for V/Q Lung Imaging

Elizabeth Bailey ¹

To understand the current role of V/Q imaging in clinical practice including suggested acquisition and processing protocols. A review of current best practice including new and innovative clinical applications for the V/Q SPECT/CT will be presented with clinical cases and research data presented. By the end of this presentation, the attendees will be aware of non-PE indications for V/Q imaging and a potential role of both clinical and research applications and be familiar with quantitative V/Q SPECT/CT and how it can be implemented and interpreted.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Peptide Receptor Radionuclide Therapy using [¹⁷⁷Lu]-Dota-SSR

Elizabeth Bailey ¹

The aim of the presentation is to understand the role of [¹⁷⁷Lu]-Dota-SSR in the treatment of Neuroendocrine tumours. The presentation will include an overall of the protocols, indications and patient outcomes when treating neuroendocrine tumours with Lu177-Dota-SSR. A review of current best practice and practical technical guidelines to assist technologists involved with providing a Lu177-Dota-SSR radionuclide therapy service. At the conclusion of the presentation, attendees will be familiar with current best practice protocols for the administration and monitoring of patients having [¹⁷⁷Lu]-Dota-SSR, have an understanding of the radiation dosimetry and potential side effects associated with PRRT and have the skills and knowledge needed to setup a [¹⁷⁷Lu]-Dota-SSR therapy program for the treatment of NET.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Accreditation and National Quality Health Service Standards

Colin Baker ¹

The 10 National Quality Health Service Standards (NSQHS) were developed to assist health care service providers deliver safety and quality health care to patients whilst minimising risk. Five standards were introduced initially in 2011 and later expanded to five more in 2012, based on extensive consultation and analysis of feedback from the health industry and consumers of the health service. This presentation will discuss the rationale for the development of the 10 standards by the Australian Government, how they were formulated, describe each standard in detail as practiced by health organisations now and the systems and methods employed to implement these standards in various health institutions. Also outline a statement of intent, context, criteria, items and actions for each standard and describe how the standards are utilised in the provision of imaging services and therapy, in order to improve patient care and clinical outcomes. Concerted and focussed education for healthcare service providers has been instrumental in the 10 standards being successfully implemented in hospitals across Australia. Success of large national initiatives such as the NSQHS standards depends on continuous review, gap analysis and measures to address the gaps and the government and hospital boards and executives have been reasonably successful in this regard. The 10 NHSQS standards, along with the rigorous clinical governance expected by hospital accreditation processes, provide the framework for standardised and safe practices of health care across the spectrum of health organisations in Australia and have been instrumental in developing safety and quality health systems and structured clinical governance.

References

1.National Safety and Quality Health Service Standards; September. 2012 [Google Scholar]
2.National Safety and Quality Health Service Standard 2: Partnering with Consumers Embedding Partnerships in Health Care; November. 2014 [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Positron Emission Tomography/Computed Tomography Hybrid Imaging in Oncology: Benefits for the Patient

David Binns ¹

The healthcare community quickly embraced the introduction of hybrid PET/CT scanners in the early 2000’s. CT improved specificity and overall diagnostic accuracy of PET scanning, while overall throughput, due to faster attenuation correction, amortised the cost over a larger number of patients. Over the last 15 years, CT systems have improved greatly in performance primarily due to the increased number of detector slices, dose modulation, and improved reconstruction algorithms. Scan quality has continued to improve while patient dose, in the main, has reduced or remained equivalent. Nuclear Medicine Specialists (NMS) and Nuclear Medicine Technologists (NMT) have the potential to optimise the contribution made by the CT scan. The governance of hybrid imaging must be supported by health services, and it is highly recommended that Molecular Imaging (MI) departments structure a multidisciplinary group that ensures best practise from both MI and Radiology sectors. The underlying impetus should always be patient benefit and safety. Oncology patients have benefitted greatly from hybrid imaging-the additional CT data improves the diagnostic accuracy of the PET scan, and patient safety is not compromised. Management by an appropriately qualified multidisciplinary team is essential to ensure the development of safe and optimum hybrid imaging protocols.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

A Paradigm Shift: Technologist Advanced Practice and Career Development-the European perspective

Pedro Fragoso Costa ¹

The role of the Nuclear Medicine Technologist (NMT) is changing. It has been changing in the last decades and adapting to the ever-evolving technologic field. The EANM Technologist Committee (EANM-TC) has worked with European partners, in order to achieve a harmonised and European definition of the NMT. For this purpose, the European Qualification Framework (EQF) was used following a number of items divided in Knowledge/Skill/Competencies (SKC). It was defined that the core competencies of a NMT were equivalent to the academic Bachelor degree. Advanced practice can be achieved, for example, through a master’s programme, but there is no European framework that recognises this level of competencies for Technologists, at the moment. There are, however, several countries that recognise this advanced practice and, given the proper education their involvement in multidisciplinary tasks. While it might be discussable for practitioners from different countries if one or the other task can be considered beyond the core competencies, it is fundamental for the discussion of advance practice, to identify and define those skills and practices according to the EQF system. Nowadays, the myriad of options for technologists will certainly relax the rigidity of competencies such as to limit or extend them, facilitating a multidisciplinary teamwork and ensure the best clinical practice towards patients. The objective of this session is to briefly present the system of qualifications in Europe, while describing the different carrier paths available to European Nuclear Medicine Technologists and EANM-TC‘s contribution in formalising some of those paths.

References

1.Waterstram-Rich K, Hogg P, Testanera G, Medvedec H, Dennan SE, Knapp W, et al. Euro-American discussion document on entry-level and advanced practice in nuclear medicine. J Nucl Med Technol. 2011;39:240–8. doi: 10.2967/jnmt.111.096354. [DOI] [PubMed] [Google Scholar]
2.Fragoso Costa P, Santos A, Testanera G. An insight into the EANM technologist committee benchmark document on nuclear medicine technologists'competencies. Eur J Nucl Med Mol Imaging. 2017;44:1604–6. doi: 10.1007/s00259-017-3741-1. [DOI] [PubMed] [Google Scholar]
3.EANM Technologist Committee. EANM Benchmark Document on Nuclear Medicine Technologists'Competencies. [Last accessed on 2018]. Available from: http://www.eanm.org/content-eanm/uploads/2016/11/EANM_2017_TC_Benchmark.pdf . [DOI] [PubMed]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Globilisation

Geoff Currie ¹

Globalization is the response to global trends. One aspect of globalization is internationalization, which is a strategic approach adopted to respond to the global market. Motivations will vary amongst countries and between individual institutions, but include commercial advantage, market share of fiscal and knowledge economies, and enhancement of outcomes. Mobilization offers a powerful tool for enhancing internationalization strategies. Here we explore the foundations of globilization, internationalization and monilization as a foundation for further exploration of impacts in nuclear medicine in the next session.

References

1.Currie G, Green LD, Wheat J, et al. Internationalisation, mobilisation and social media in higher education. J Med Imaging Rad Sci. 2014;45:399–407. doi: 10.1016/j.jmir.2014.03.094. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Partnering

Geoff Currie ¹

This session explores strategies for effective partnering and productive partnerships to overcome geographic and professional isolation. We explore key factors in identifying suitable partners and mechanisms for partnering success. This session builds on globilization, internationalization, and monolization previously discussed and explores challenges in delivering a package through partnership for overcoming geographic and professional isolation.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Craft of Medical Radiation Science

Geoff Currie ¹

In Medical Radiation Science, the “art” of our profession lies in intuition which is informed by science, education, and experience. Art or intuition recognises that the end product or outcome can be very variable and defined by our sense or feeling that the task is done. On the other hand, “science” is informed by evidence, technology, and defined protocols. The end points tend to be reproducible and defined by a predefined expected outcome; “it worked” rather than “it feels right”. In Medical Radiation Science we bring art and science together to define pour profession. If we get the balance of art and science right, it is more than a profession; it’s a “craft”. Professionalism is a “craft” (clinical, research, invention, innovation, education, patient care, instrumentation, and so on). To craft a career implies both the use of logic and intuition. Magic is a craft; the application of science and art to create an illusion that would not have the outcomes expected if it relied on either art or science alone. Medical Radiation Science demands a balance along a continuum in the command and exploitation of both art and science. Arthur C. Clarke once said “any sufficiently advanced technology is indistinguishable from magic” The craft of Medical Radiation Science is to make the magic tangible.

References

1.Currie G. The art/science continuum. J Med Imaging Radiat Sci. 2014;45:352–3. doi: 10.1016/j.jmir.2014.02.003. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Innovation in Positron Emission Tomography/Computed Tomography: New, Now and Next

Scott Evans ¹

The aim of this session is to describe new technologies and applications of PET and to review the future directions. Recently introduced methods of PET image acquisition and processing will be discussed. Alternate utilisation of regular tracers and future applications of new PET tracers will be reviewed. New technologies and applications in PET provide improved imaging and clinical outcomes. Improved imaging and diagnostic outcomes can be achieved by utilising new technologies and applications in PET.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Advanced Practice: An International Perspective

Karren Fader ¹

Globally, advanced practice medical radiation technologist (APMRT) come in many forms.[1] The models of advanced practice are as varied as the names we choose to call ourselves. They may evolve as a natural consequence to a need or could be intentionally determined then developed. Some countries models of advanced practice have been around for decades, while others have been recently created and implemented. Regardless of difference in these areas, when an advanced practice role is generated, fundamental principles are required for the framework.[2] Core competencies or pillars are the foundation of advanced practice models. Individual core competencies of advanced practice may use different terms but are based on the same premise or concept. Generally, they fall within the areas of: autonomy or independent decision making regarding patient management, higher learning or graduate level education, clinical expertise in a specific area, leadership in practice and engaging in research. The combination of honed skills and enriched attributes is the hallmark of an advanced practitioner. There are differing positions on what is an acceptable purpose or use of the role of advanced practice.[3] However, a positive impact, directly or indirectly, on the patient and/or system is possible and important to demonstrate. Challenges to advanced practice are best addressed by conducting research to provide evidence of value.[4]

References

1.Hardy M, Legg J, Smith T, et al. The concept of advanced radiographic practice: An international perspective. Radiography. 2008;14:e15–9. [Google Scholar]
2.Price RC, Edwards HM. Harnessing competence and confidence: Dimensions in education and development for advanced and consultant practice. Radiography. 2008;14:e65–70. [Google Scholar]
3.Mafi JN, Wee CC, Davis RB, Landon BE. Comparing use of low-value health care services among U.S. advanced practice clinicians and physicians. Ann Intern Med. 2016;165:237–44. doi: 10.7326/M15-2152. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Hardy M, Johnson L, Sharples R, Boynes S, Irving D. Does radiography advanced practice improve patient outcomes and health service quality?A systematic review. Br J Radiol. 2016;89:20151066. doi: 10.1259/bjr.20151066. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Educating Medical Imaging Technologists: Science v Art

Daphne James ¹

This presentation will discuss the nexus of science and art in the education of medical imaging technologists in Australia. Medical Radiation Science programs in Australia are built on a foundation of basic science, interwoven with the development of profession-specific knowledge and clinical skills. Science and art in all aspects of medicine are supplementary to each other. The art of our professions is centred in patient care and in the subtle nuances required for the development of clinical skills. Education providers use simulated learning activities to prepare students for clinical practice in areas such as communication skills, venepucture, and image interpretation. Clinical supervision and assessment requires practitioners to make subjective judgements and assess students’ practical performance. Clinical educators need to develop effective skills to ensure students are given quality feedback and have a successful clinical experience.

References

1.Raab K. Mindfulness, self-compassion, and empathy among health care professionals: A review of the literature. J Health Care Chaplain. 2014;20:95–108. doi: 10.1080/08854726.2014.913876. [DOI] [PubMed] [Google Scholar]
2.Thoirs K, Giles E, Barber W. The use and perceptions of simulation in medical radiation science education. Radiographer. 2011;58:5–11. [Google Scholar]
3.Reid-Searl K, Bowman A, McAllister M, Cowling C, Spuur K. The masked educator-innovative simulation in an Australian undergraduate medical sonography and medical imaging program. J Med Radiat Sci. 2014;61:233–40. doi: 10.1002/jmrs.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Francis A, Hills C, MacDonald-Wicks L, et al. Characteristics of an ideal practice educator: Perspectives from practice educators in diagnostic radiography, nuclear medicine, nutrition and dietetics, occupational therapy and physiotherapy and radiation therapy. Radiography. 2016;22:287–94. [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

New technologies and Applications in Nuclear Medicine: What’s New in Single Photon Emission Computed Tomography/Computed Tomography

Peter Kench ¹

It’s now more than thirty years since the introduction routine clinical SPECT imaging in the 1980’s, what will the new generation SPECT imaging look like? For decades, most SPECT gamma cameras have been comprised of two rotating collimated detectors positioned at 90 or 180 degrees. The addition of CT to SPECT saw significant improvements in diagnostic accuracy due to accurate correction of photon attenuation and a better knowledge of the radiopharmaceutical localisation. For many clinical applications, a single SPECT is performed to further investigate abnormal uptake seen in planar images. Investigators have demonstrated that for metastatic bone imaging, whole-body planar imaging may be replaced by whole-body SPECT for the same administered dose and imaging time, with the advantage of improved sensitivity. The implementation of quantitative SPECT for the assessment of patient dose for theranostics applications may also benefit from whole-body SPECT allowing improved calculation of therapeutic administered activity. The same technological advances that enable whole-body SPECT may also be utilised to perform dynamic SPECT. Fast rotating dual head gamma cameras may provide sufficient temporal resolution to see subtle changes in radiopharmaceutical distribution over time. Dynamic cardiac SPECT is now possible due to the unique acquisition geometry of dedicated cardiac scanners where multiple detectors surround the heart for tomography. The addition of whole-body and dynamic SPECT to conventional molecular imaging will provide the clinician with new data to aid in the accurate diagnosis of disease and planning of therapy.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Revolution of Science in Medical Radiation Science

Peter Kench ¹

Radical changes to medical radiation sciences come from the implementation of new knowledge from associated and sometimes very different fields of science. Disruptive advances in Nuclear Medicine broadly come from the advancements in the areas of: radionuclide production and chemistry; technological advances in signal processing, photon detectors, collimation and unique imaging geometries; new software algorithms that create precise images of radionuclide distribution and accurately map minute changes in molecular pathways. This presentation will examine current advances in radiopharmaceuticals, molecular imaging systems and software engineering that may result in improved healthcare and patient experience.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Cardiac Computed Tomography-Techniques and Challenges

Hannah Lane ¹

With coronary artery disease continuing to be a leading cause of death in western societies, early identification and treatment of disease is essential for positive patient outcomes. Whilst coronary angiography remains the gold standard for luminal assessment, non-invasive diagnostic imaging tests such as computed tomography (CT) are increasingly being utilised in the assessment of coronary artery disease and cardiac function. The technology in this field is rapidly evolving, enabling lower radiation doses for higher resolution images and widespread accessibility. This presentation aims to provide a brief overview of the history of cardiac imaging, discuss the challenges associated with cardiac CT and techniques to overcome these. The advantages and disadvantages of CT will be contrasted with other cardiac imaging modalities such as magnetic resonance imaging (MRI) and nuclear myocardial perfusion studies.

References

1.CSANZ Guidelines –Noninvasive Coronary Artery Imaging: Current Clinical Applications. 2010 [Google Scholar]
2.CSANZ Guidelines –Coronary Artery Calcium Scoring –Position Statement. 2017 [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

The Old and New Artefacts of Single Photon Emission Computed Tomography/Computed Tomography Imaging

Darin O’Keeffe ¹

Optimal radiopharmaceutical and administered activity selection are the first elements for successful SPECT imaging. SPECT imaging also places great demand upon the performance of the gamma camera system and requires adherence to assumptions made for the purpose of image reconstruction, such as that the radioactivity distribution will remain static during the acquisition. When the performance of the imaging system diminishes, or the assumptions are violated, SPECT image quality is compromised and artefacts can arise. The addition of a CT acquisition for anatomical localisation or attenuation correction adds its own performance requirements and set of assumptions when the CT data is used to derive linear attenuation coefficients for attenuation correction. Artefacts in the CT scan can propagate into the SPECT images and obscure or even mimic pathology. In this presentation we briefly visit some of the artefacts that have plagued SPECT imaging since its early development, such as patient motion and gamma camera non-uniformity. We then work through a selection of common SPECT and SPECT/CT-specific artefacts, formulating a mindset to help recognise and prevent or minimise such artefacts.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

¹⁷⁷Lu-Prostate Specific Membrane Antigen Theranostics – A 50 Patient Introduction

Mark Scalzo ¹

With a long standing Peptide Receptor Radionuclide Therapy (PRRT) program for Neuroendocrine Tumours (NETs), Peter MacCallum Cancer Centre was well established to add to its theranostic arsenal. Utilising radiolabelled Prostate Specific Membrane Antigen (PSMA) under trial conditions has been a process of evolution in treating patients with advanced prostate cancer - who have failed other forms of conventional therapies including chemotherapy and radiotherapy. The aim of this presentation is to describe the relationships between three distinctive diagnostic imaging radionuclides [⁶⁸Ga-PSMA, ¹⁸F-FDG & ^99mTc-MDP] and the two Nuclear Medicine imaging techniques [PET/CT and SPECT/CT] and their role in determining a patient’s suitability for treatment with ¹⁷⁷Lu-PSMA. Workflow considerations relating to the administration and post-therapy imaging of 177Lu-PSMA will also be discussed as part of the desired learning objectives.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Advances in Detector Technology in Nuclear Medicine and Hybrid Imaging

S Somanesan ¹

A review of Nuclear Medicine and PET detectors will be initially undertaken to give participants an idea of the advancement and historical development of these detectors. The replacement of scintillation/PMT detector system will be discussed in detail with reasons for their change, developments and current trends in detector technology would be covered. A review of solid-state detector technology that was approved by the FDA in 1997 will be provided. The high cost and sporadic ability of CZT crystals with limited adoption by the majority of companies & use in large FOV scanners will be discussed besides the long replacement cycles and substantial cuts in reimbursement that may have had a stronger adverse impact on technology adoption than previously expected will be delved into. The strong driver for solid-state technology being its ability to be coupled with other imaging modalities, such as MRI and in addition, solid-state detectors that have good low-energy resolution and are sensitive to a wider range of energies will be looked at as well. What is in the market now for hybrid SPECT/CT, PET/MR & PET/CT scanners would be discussed before summarising.

References

1.Lewellen TK. Recent developments in PET detector technology. Phys Med Biol. 2008;53:R287–317. doi: 10.1088/0031-9155/53/17/R01. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Jaszcak RJ. The early years of single photon emission computed tomography: An anthology of selected reminiscences. Phys Med Biol. 2006;51:R99–115. doi: 10.1088/0031-9155/51/13/R07. [DOI] [PubMed] [Google Scholar]
3.Lewellen TK. Recent developments in PET detector technology. Phys Med Biol. 2008;53:R287–317. doi: 10.1088/0031-9155/53/17/R01. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Huizengan J, Seifurt S, Schreuder F, et al. A fast preamplifier concept for SiPM-based time-of-flight PET detectors. Nucl Instrum Methods Phys Res. 2012;695:379–84. [Google Scholar]
5.Madsen MT. Recent advances in SPECT imaging. J Nucl Med. 2007;48:661–73. doi: 10.2967/jnumed.106.032680. [DOI] [PubMed] [Google Scholar]
6.Peterson TE, Furenlid LR. SPECT detectors: The anger camera and beyond. Phys Med Biol. 2011;56:R145–82. doi: 10.1088/0031-9155/56/17/R01. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Roncali E, Cherry SR. Application of silicon photomultipliers to positron emission tomography. Ann Biomed Eng. 2011;39:1358–77. doi: 10.1007/s10439-011-0266-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Quality Management in Nuclear Medicine

S Somanesan ¹

Aspects of Quality Management pertaining to Nuclear Medicine imaging and radionuclide therapy will be discussed in this presentation based on the international best practice and the IAEA QUANUM process. The IAEA QUANUM checklist will be described and how it can be adapted to suit a Nuclear Medicine facility will be discussed. A mock Quality Management audit will be role played to describe the process better.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Paediatric Positron Emission Tomography/Magnetic Resonance Imaging

Duncan Veysey ¹

To provide a high quality, efficient, paediatric PET/MRI service, a Medical Imaging Department must understand and establish dedicated paediatric processes prior to implementation and service provision. Based on the experience of over 650 clinical paediatric examinations, our Institution has learnt a number of important lessons integrating PET/MRI into an imaging department. To utilise the advantages of PET/MRI for paediatric populations whilst providing a safe and high quality service, an understanding of the workflow differences of PET/MRI compared with PET/CT is required. Paediatric patients require patient-focussed care, incorporating individualised preparation and assessments, together with protocol designs and imaging sequences from an integrated team of Nuclear Medicine and MRI backgrounds. It is recognised that there are significant potential advantages of PET/MRI for paediatric populations.[1,2] These advantages include reduced radiation dose to the patient, attendance for a single appointment whereby dedicated three-dimensional MR imaging is often required concurrently, a reduction in sedation or general anaesthesia events, and potential for increased resolution and reporting confidence from a concurrently acquired diagnostic MRI. Other resources that are integral to a paediatric PET/MRI team, often required on short notice, include educational play therapy (EPT), pharmacological pain relief and/or sedation, general anaesthesia, vendor support, and referrer engagement. PET/MRI is an evolving field, with improvements, developments, and challenges to overcome daily. Paediatric patients add a whole gamut of emotions to demand all of your skills as a technologist. As equally as paediatric PET/MRI can be frustrating and emotional, it is satisfying, personal, and continually challenges you to provide excellence for your patient. Technological considerations are continually changing, and demand a flexible, team approach.

References

1.Bailey DL, Antoch G, Bartenstein P, Barthel H, Beer AJ, Bisdas S, et al. Combined PET/MR: The real work has just started. Summary report of the third international workshop on PET/MR imaging; February 17-21 2014, Tübingen, Germany. Mol Imaging Biol. 2015;17:297–312. doi: 10.1007/s11307-014-0818-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Gatindis S, Bender B, Reimold M, Schafer JF. PET/MRI in children. Eur J Radiol. 2017;94:A64–70. doi: 10.1016/j.ejrad.2017.01.018. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

It’s a No-Brainer: Why, What and how to Perform Quantitative Positron Emission Tomography Imaging for Neuroscience Research and Clinical Trials

Rob Williams ¹

Neurological PET has changed beyond FDG and visual image reporting. PET scanning is now used to, screen and guide therapeutics for many neurological diseases. We have pragmatically optimised our procedures to balance accuracy, patient needs, research costs, and isotope availability and decay characteristics. This presentation will cover the technical elements that are key to Neuro PET studies. This will include quality control of instrumentation, the importance of patient preparation, and injection procedures. We will include tips for patient positioning and how to maximise technical image quality while reducing subject movement. From a technical perspective, we will discuss how to best perform imaging to match the project and the particular scanner. In longitudinal studies efficient and accurate record keeping is vital, data curation and backup, ways of doing this will also be discussed. The presentation will summarise the most common problems and the take-home tips and tricks for performing best practice neurological PET.

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

ASNM Cognitive Symposium: Amyloid Positron Emission Tomography in Vascular Cognitive Impairment

Vincent Mok ¹

Cognitive impairment is a very frequent sequel after stroke. The mechanisms explaining cognitive impairment post-stroke can be multiple, and can be related to the size and site of the stroke lesion.[1] Since autopsy studies also suggested that mixed amyloid and cerebrovascular disease is a common cause for dementia, concurrent Alzheimer’s pathology in subjects with stroke may also account for the cognitive impairment after stroke1. However, before the availability of amyloid PET, determining the presence of Alzheimer’s pathology in subjects with stroke was not easy. Our Centre is the first group in the world that utilized Pittsburgh Compound B (PiB) PET imaging in the evaluation of cognitive impairment after stroke.[2] We found that concurrent presence of significant PiB retention was present in about 30% of subjects with new onset dementia post-stroke/transient ischemic attack (TIA)[3,4] and its presence was associated with a rapid decline in cognition over the long term.[5] Interestingly, we also found that TIA was able to trigger the onset of dementia in subjects harbouring significant amyloid burden.[1] In general, subjects harbouring significant amyloid burden had a higher prevalence of Apoe4 polymorphism and slightly lesser vascular burden.[3] However, in the absence of amyloid PET, determining the presence of amyloid burden in majority of subjects with stroke/TIA was not easy. Overall, amyloid PET has an important role in the management of post-stroke/TIA cognitive impairment as presence of significant amyloid burden will influence the prognosis as well as the treatment for post-stroke/TIA cognitive impairment.[6]

References

1.Mok VC, Lam BY, Wong A, Ko H, Markus HS, Wong LK, et al. Early-onset and delayed-onset poststroke dementia –Revisiting the mechanisms. Nat Rev Neurol. 2017;13:148–59. doi: 10.1038/nrneurol.2017.16. [DOI] [PubMed] [Google Scholar]
2.Mok V, Leung EY, Chu W, Chen S, Wong A, Xiong Y, et al. Pittsburgh compound B binding in poststroke dementia. J Neurol Sci. 2010;290:135–7. doi: 10.1016/j.jns.2009.12.014. [DOI] [PubMed] [Google Scholar]
3.Yang J, Wong A, Wang Z, Liu W, Au L, Xiong Y, et al. Risk factors for incident dementia after stroke and transient ischemic attack. Alzheimers Dement. 2015;11:16–23. doi: 10.1016/j.jalz.2014.01.003. [DOI] [PubMed] [Google Scholar]
4.Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: A meta-analysis. JAMA. 2015;313:1939–49. doi: 10.1001/jama.2015.4669. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Liu W, Wong A, Au L, Yang J, Wang Z, Leung EY, et al. Influence of amyloid-βon cognitive decline after stroke/Transient ischemic attack: Three-year longitudinal study. Stroke. 2015;46:3074–80. doi: 10.1161/STROKEAHA.115.010449. [DOI] [PubMed] [Google Scholar]
6.van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impairment. Nature Rev Dis Prim. 2018;4:18004. doi: 10.1038/nrdp.2018.3. [DOI] [PubMed] [Google Scholar]

World J Nucl Med. 2018 Sep;7(Suppl 1):S1–S48.

Dissociation of Brain Atrophy Measured by Magnetic Resonance Imaging and Regional Tau Deposits Measured by ¹⁸F-THK5351 Positron Emission Tomography

Hiroshi Matsuda ¹

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects. The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using ¹⁸F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had no effect on the precision of tau load measures. Grey matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, no correlation was found between atrophy and tau deposits, even after PVC. PVC did not significantly affect ¹⁸F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.

References

1.Maass A, Landau S, Baker SL, et al. Alzheimer's Disease Neuroimaging Initiative –Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease. Neuroimage. 2017;157:448–463. doi: 10.1016/j.neuroimage.2017.05.058. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref1] 1.Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics–2015 update: A report from the American Heart Association. Circulation. 2015;131:e29–322. doi: 10.1161/CIR.0000000000000152. [DOI] [PubMed] [Google Scholar]

[ref2] 2.Wilmot KA, O'Flaherty M, Capewell S, Ford ES, Vaccarino V. Coronary heart disease mortality declines in the United States from 1979 through 2011: Evidence for stagnation in young adults, especially women. Circulation. 2015;132:997–1002. doi: 10.1161/CIRCULATIONAHA.115.015293. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref3] 3.Shaw LJ, Kohli P, Chandrashekhar Y, Narula J. Cardiovascular imaging of women: We have come a long way but still have a ways to go. JACC Cardiovasc Imaging. 2016;9:502–3. doi: 10.1016/j.jcmg.2016.02.012. [DOI] [PubMed] [Google Scholar]

[ref4] 4.Schulman-Marcus J, Hartaigh BÓ, Gransar H, Lin F, Valenti V, Cho I, et al. Sex-specific associations between coronary artery plaque extent and risk of major adverse cardiovascular events: The CONFIRM long-term registry. JACC Cardiovasc Imaging. 2016;9:364–72. doi: 10.1016/j.jcmg.2016.02.010. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref5] 5.Baldassarre LA, Raman SV, Min JK, Mieres JH, Gulati M, Wenger NK, et al. Noninvasive imaging to evaluate women with stable ischemic heart disease. JACC Cardiovasc Imaging. 2016;9:421–35. doi: 10.1016/j.jcmg.2016.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

INVITED ORAL PRESENTATIONS

Cardiology: What’s Best for Women in 2018?

Paula Averbuj

References

Anatomy versus Function Investigate Chest Pain

Barry Elison

Read with the Experts – Heart Failure and I-123 Meta-Iodobenzylguanidine

Kenichi Nakajima

References

Current Status and Local Challenges in Asia

Kenichi Nakajima

References

The Impact of Coronary Calcium Score as an Addition to Myocardial Perfusion Imaging in Altering Clinical Management

Stephen Stowers

References

Endocrinology: What’s New in Adult Thyroid Cancer Management

Jeremy Hoang

Nuclear Medicine and Hyperparathyroidism

Ivan Ho Shon

References

Radioiodine in the Management of Benign Thyroid Disease: A Practical Australian Approach

W John McKay

References

F-Fluoro-L-Dihydroxyphenylalnine Imaging in Hypoglycaemia of Infancy

David A Pattison

Reference

SPECT/CT and PET/CT Imaging in Thyroid Cancer

Ka Kit Wong

Reference

Infection/Inflammation: Molecular Imaging in Diabetic Patients with Infection

Edel Noriega Álvarez, ISORBE

References

Imaging Fungal Infections

Alfred Ankrah

References

Update on HIV: Prevention, Treatment and Cure

James cmahon

White Blood Cell Labeling: Pearls and Pitfalls

Kutlan Ozker

References

Molecular Imaging of Infection in the Prosthetic Joint

Christopher J Palestro

Reference

Imaging Tuberculosis

Mike Sathekge

References

Imaging of Atherosclerosis

Helmut Sinzinger

References

Which, Where and When to Select Radioantibiotics, Labelled Leucocytes and Radiolabelled Peptides for Infection/Inflammation

Victoria Soroa

References

Tracking Virus Infection and Immune Responses In Vivo: From Macro to Microscopic Characterization

Francois Villinger

References

Imaging Vascular Graft Infection

Mariza Vorster

References

Molecular Imaging: Multimodality Imaging

Weibo Cai

Reference

When Particles Meet…. Interaction of Radiation with Nanoparticles

Jan Grimm

Probe Development – Small Molecule Agents in Neuroscience

Michael Kassiou

Reference

Molecular Imaging Probe Development – Nanoparticles

Dong Soo Lee

Reference

Measuring the Dopamine Response to Cigarette Smoking in Men and Women with “lpntPET”: Tuning the Kinetic Model to Capture Dopamine Fluctuations

Evan Morris

Molecular Imaging Probe Development-Reporter Genes

Hyewon Youn

Reference

Musculoskeletal: Bone Scanning in Relation to Hip Prostheses

Stephen Allwright

Reference

Update on Radiosynovectomy for Hemophilic Arthropathy and Rheumatoid Arthritis

Emerita Barrenechea

Oncology: Colorectal Carcinoma: Treat with the Experts-Regional treatment with ⁹⁰Y-SIRspheres