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. 2011 Jan-Jun;10(1):98–107.

Abstracts of Poster Presentations (PRRNT)

PMCID: PMC3198047
World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-043: Peptide Receptor Radionuclide Therapy in Patients with Carcinoid Heart Disease (Hedinger's Syndrome): Prognostication of Efficacy by Ga-68 SMS Receptor PET/CT

Vikas Prasad, M. Secknus, D. Hoersch, T. Kuntze, Kulkarni H., C. Zachert, R.P. Baum

Zentralklinik, Bad Berka, Germany

Aims:

The objectives of the study were to determine the survival in patients with carcinoid heart disease (Hedinger's Syndrome, HS) and to analyse the efficacy of Peptide Receptor Radionuclide Therapy (PRRNT) with Y-90 or Lu-177 DOTATATE in these patients.

Materials and Methods:

Out of 550 patients with progressive neuroendocrine tumors treated at our neuroendocrine tumor centre, 42 patients (mean age 59 years; Female: Male 19:23) were found to have HS (confirmed by 2-D echocardiography and Colour Doppler). Patients were treated with either Y-90 or Lu-177 DOTATATE at 3-4 months intervals under amino acid nephroprotection and 3-monthly serotonin level monitoring. Response was assessed by Ga-68 DOTANOC receptor PET/CT. Kidney function was assessed using renal scintigraphy (Tc-99m MAG3) and tubular extraction rate (TER), and glomerular filtration rate measurements using single sample plasma clearance method.

Results:

Out of the 42 patients with HS, 23 patients had NET of the ileum/jejunum/stomach, 14 had pancreatic NET, 4 with Carcinoma of Unknown Primary (CUP), and one had rectal NET. According to severity, 17 patients had grade I, 8 grade II, 4 grade III and 13 had grade IV tricuspid valve regurgitation (TR). 9/42 (21%) patients died. Median/mean survival from time of first diagnosis (ToFD) in patients with high grade TR (grade 3 and 4) was 146/123 months as compared to a mean survival time of 233 months for low grade (1 and 2) TR from ToFD. Mean survival in patients with high grade TR was 33.8 months from the time of first PRRNT (42% died) vs. 69.3 months for low grade TR (7% died). Patients treated with 3 cycles of PRRNT achieved stable disease (SD) in 50% while the remaining had progressive disease (PD). 6 patients had improvement in TR after PRRT (all with grade 1). Four patients with grade 4 TR underwent tricuspid valve replacement. Mean fall in TER (32.6%) was significantly higher as GFR fall (26%) suggesting that TER may be a better predictor of renal function in patients with HS. There was a significant correlation between the grade of TR and TER value (n=30); no correlation was observed concerning GFR and grade of TR. TER fall (16.2%) in low grade TR was significantly lower as compared to TER fall (37.5%) in patients with high grade TR; no such correlation was observed for GFR.

Conclusions:

The probability of survival in patients with high grade HS is two times lesser when compared to those with low grade HS. Patients with carcinoid heart disease have poorer response to PRRNT as compared to patients with normal heart function. Tubular extraction rate is the better parameter for assessment of renal function in carcinoid heart disease.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-044: Y90 and Lu177 DOTATATE Targeted Radionuclide Therapy for Neuroendocrine Tumors: Review of 3 years Experience

Sobhan Vinjamuri, A. Sreedasyam, M. Pritchard, P. Maltby, G. Poston

Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK

Introduction:

Targeted radionuclide therapy represents a key area for growth in nuclear medicine. However, the lack of structured protocols for assessment of patients, treatment regimens, availability of local expertise and funding disparities has resulted in a disproportionate distribution of centres performing these procedures.

Aims/ Objectives:

To review our clinical experience over the past 3 years and understand the side effect profile of the two therapeutic procedures in a clinical series, thereby enhancing the evidence base in this complex area of medicine.

Materials and Methods:

A retrospective database review was conducted based on information readily available. Decisions on Y90 v Lu177 DOTATATE therapy were reviewed. Side effect profile was catalogued for 10 weeks post administration and delayed side-effects were reviewed in the clinical context by the treating team. As part of a shared care programme, the referring hospital retained key responsibility for the patient while the treating team retained responsibility for the treatment related issues. Post-treatment letters identifying treatment response and maintenance of remission are logged when available. Survival data were checked on Hospital Information Systems just prior to data analysis.

Results:

While the shared care system provides good continuity of care to patients, the lack of direct and continuing responsibility of the treating team has resulted in huge gaps in follow-up data. The incidence of side effects using this shared care approach is relatively low with only 2 patients developing delayed myelotoxicity and 1 patient developing chronic renal dysfunction in the past 12 months. Where radiological response is well demonstrated (such as progression or partial response on CT), this is well documented and communicated to the treatment team. However, the lack of recording of improvement in symptoms of carcinoid syndrome by some teams means that vital subjective patient data cannot be captured and logged. In the absence of automatic updates of clinical databases, Survival data currently can only be performed by spot-checking on hospital information systems, and this again can lead to some inconsistencies of data collection and analysis.

Conclusion:

From our experience the area of targeted radionuclide therapy can be improved by the following: 1) A standardised approach to selection of patients for Y90 or Lu177 DOTATATE targeted radionuclide therapy; 2) Although the side effect profile with Lu177 DOTATATE is lower, there is significant improvement in a few patients after receiving Y90 DOTATATE, and this procedure has its value.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-045: 177Lu-DOTA-TATE in Peptide Receptor Radionuclide Therapy: First Year Experience in Turkey

Levent Kabasakal1, Emre Demirci1, Meltem Ocak2, Clemens Decristoforo3, Çiğdem Papilla4, Ahmet Araman2, İlhami Uslu1

1Department of Nuclear Medicine, Cerrahpaşa Medical Faculty, Aksaray Istanbul, Turkey; 2Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, Istanbul, Turkey; 3Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria and 4Department of Internal Medicine, Division of Medical Oncology, Cerrahpaşa Medical Faculty, Aksaray, Istanbul, Turkey

Aim of the Study:

Initial treatment for patients with inoperable metastatic neuroendocrine tumors (NET) has been started with high doses of 111In-DTPA-octreotide (Octreoscan). 111In-coupled peptides were found not ideal for peptide receptor radionuclide radiotherapy (PRRT) because of the small particle range and short tissue penetration. Therefore 90Y-DOTATOC was developed. After this achievment 177Lu-DOTATATE was also shown to be very successful in tumor regression. Therefore we have started to treat inoperable NET patients with 177Lu-DOTATATE and in this study we aimed to present the first datas on side-effects of the treatment.

Materials and Methods:

From May 2010 to February 2011, 26 patients (mean age 50.88±13.87, F/M: 14/12, 186±36mCi) have received 36 therapy doses. As a renal protection i.v. infusion of amino acid solution were used during the treatment sessions. Initial side effects, haematological and renal parameters were monitored before and after therapy.

Results:

After therapy 27% of patients had nausea/vomiting, 17% patients had hair loss. No significant difference was observed with levels of urea, creatinin and white blood, platelet, hematocrit counts after therapy (P>0.05). But a significant decrease in lymphocyte count was observed (P<0.05). Three patient died during follow up before having second therapy.

Summary:

177Lu-DOTATATE therapy has been started safely and efectively in our department for the patients who have no therapeutic options.

Acknowledgments

This work was part of COST Action BM0607 “Targeted Radionuclide Therapy”.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-046: Indian Patients of Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastasis Treated with 177 Luthetium DOTATATE Therapy- Response Profile

Shefali Gokhale1, B.A. Krishna2, Meera Venkatesh3, S.D. Salunkhe4, A. Mulay5, T. Das3, S. Banerjee3, M. Vyas2, A. Rafi1

1Nuclear Medicine, Inlaks and Budhrani Hospital, Pune, 2Nuclear Medicine, Hinduja Hospital and Research Centre, Mumbai, 3Radiopharmaceutical Division, BARC, 4Surgical Gastroenterology, Inlaks and Budhrani Hospital, Pune, 5Nephrology, Inlaks and Budhrani Hospital, Pune, India

Aim:

Peptide receptor radionuclide therapy (PRRT) with 177 Luthetium (Lu) DOTATATE is being used for treating metastatic gastroenteropancreatic (GEP) neuroendocrine tumors (NET) with promising results in terms of the primary end point of survival benefit after four treatment cycles.

This is a prospective study to analyse the response profile in Indian patients of GEP NET with liver metastasis. In this pilot study, we report our findings on the secondary end points of tumor regression and symptom resolution.

Materials and Methods:

A total of 11 patients of GEP NET with liver metastasis, (9 males, 2 females), in the age group 41 - 71 years were treated with 177 Lu DOTATATE therapy from September ’2009 to December ’2010. All of these patients were not responding to long acting octreotide injections. All the patients were found to have tracer avid lesions on Somatostatin Receptor Imaging (SRI). Patients underwent a thorough clinical evaluation with appropriate investigations prior to therapy. All these patients had a compromised liver reserve.

177Luthetium was obtained as 177 Luthetium Chloride from the Radiopharmaceutical division of BARC. In-house labeling of 177 Lu with DOTATATE was done. In view of the compromised liver reserve, a smaller dose of 80 -120 mCi 177 Lu DOTATATE was administered intravenously over 30 minutes along with aminoacid co-infusion. The patients were offered 4 treatment cycles at a gap of 6 weeks, however, they opted for one to two treatment cycles. The patients were followed up with clinical assessment and radiological work up 12-16 weeks after therapy.

Result:

Of the 11 patients treated, 6 patients were symptomatic at presentation. Three patients (50% of the symptomatic group) responded well to therapy in terms of either reduced tracer avidity on Somatostatin Receptor Imaging on qualitative assessment or central necrosis of lesions on CT Scan. All these patients had relief from symptoms. One patient responded well to the first therapy, however deteriorated clinically after the second therapy was administered. Of the five asymptomatic patients treated, three died of liver failure and two patients developed symptoms, such as loose stools and flushing.These two patients did not undergo follow up investigations.

Summary:

In Indian patients of gastroenteropancreatic (GEP) neuroendocrine tumor with symptomatic liver metastasis, 177 Lu DOTATATE therapy is a potential therapeutic tool even when they have a compromised liver reserve. It produced a functional regression of lesions as well as good symptomatic relief at the end of even 1-2 treatment cycles. In a patient paid program like ours, we could use these results to motivate patients to undergo further treatment cycles.

However, its role in asymptomatic GEP neuroendocrine tumor patients with liver metastasis, needs to be studied further with a larger number of patients. Whether even smaller but multiple dose treatment cycles would benefit asymptomatic patients of GEP NET with liver metastasis and poor liver reserve needs to be investigated further.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-047: Neoadjuvant Peptide Receptor Radionuclide Therapy for an Inoperable Neuroendocrine Pancreatic Tumor

Kämmerer, V. Prasad, G. Klöppel, W. Daffner, D. Hörsch, M. Hommann, R.P. Baum

Zentralklinik, Bad Berka, Germany

Pancreatic endocrine tumors (pNETs) are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis many of them are already advanced and difficult to treat. We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman, who received neoadjuvant peptide receptor radionuclide therapy (PRRT) as first-line treatment. This resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal. Follow-up for eighteen months revealed a complete remission. This is the first report on neoadjvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-048: 68Ga -DOATATE PET/CT: Semi-Quantitative Analysis of Physiological and Pathological Uptake Using SUV

Jolanta Kunikowska1, Leszek Krolicki1, Dariusz Pawlak2, Imene Zerizer3, Renata Mikołajczak2, Piotr Czwarnowski1

1Nuclear Medicine Department, Medical University of Warsaw, Poland, 2IEA POLATOM, Świerk, Poland and 3Imperial College Health Care NHS Trust, United Kingdom

Aim:

Neuroendocrine tumors (NETs) are a rare type of cancer that originates from the hormone-producing cells of the neuroendocrine system. Most of these are characterized by overexpression of somatostatin receptors (SSTR). Positron emission tomography (PET) combined with computer tomography (CT) using 68Ga-DOTATATE is a promising method for the evaluation of patients suspected of having NET; therefore, knowledge of normal and pathological 68Ga -DOTATATE uptake is necessary for accurate interpretation. The aim of this study was to define sites of physiological and pathological uptake of 68Ga-DOTATATE using semiquantitative analysis (SUVmax).

Materials and Methods:

We retrospectively reviewed 68Ga-DOTATATE PET/CT studies performed at our institution in 230 patients (70 men, 160 women, mean age 53.2±13.9, age range 18-86). Patients were images on a Biograph 64 TruePoint (Siemens Medical Solutions) PET-CT scanner 60-80 minutes post injection of 120-200 MBq 68Ga - DOTATATE. Clinical history, previous imaging examinations and treatments were recorded. Images were reviewed by an experienced investigator using the Siemens workstation and SUVmax measurements were performed using a small region of interest (ROI) for physiological uptake over the pituitary gland, thyroid, salivary gland, normal liver, spleen, adrenal and kidneys. In addition, SUVmax measurements were recorded for areas of pathological uptake. The mean SUVmax (±standard deviation) was determined for each region.

Results:

In disease free regions the mean SUVmax in the pituitary gland=11.4 (±5.3), thyroid=2.9 (±1.2), salivary glands=3.4 (±1.8), liver=6.6 (±2.2), spleen=18.8(±6.6), adrenal=14.3 (±3.6) and kidney=14.6 (±3.5). In addition, increased uptake in the uncinate process of the pancreas was noted in 16.1% of patients with a mean SUVmax =9.3 (±3.5).In patients with pathological sites of uptake, the SUVmax in liver=31.6 (±26.5), adrenal gland=73.2 (±37.8), bone 28.6=(±37.1), intestine 24.2=(±26.1), lung=21 (±29.1), brain=32.9 (±45.5), lymph node=28.4 (±25.9), thyroid=30.7 (±40.5), pancreas=39.9 (±37.9), peritoneum=34.9 (±40.9) and stomach=75.2 (±52.3).

Conclusion:

This study highlights important sites of physiological biodistribution of 68Ga - DOTATATE and quantified pathological uptake which is much higher than physiological uptake. Knowledge of 68Ga -DOTATATE PET/CT biodistribution and uptake values is highly important to differentiate sites of disease from normal physiological uptake.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-049: Early and Late 68Ga-DOTA-NOC PET/CT in Somatostatin Receptor SSTR Expressing Organ and Tumor

Emre Demirci1, Meltem Ocak2, Levent Kabasakal1, Clemens Decristoforo3, Yıldız Özsoy2, Ahmet Araman2, Ilhami Uslu1

1Department of Nuclear Medicine, Cerrahpaşa Medical Faculty, Aksaray Istanbul, Turkey; 2Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, Istanbul, Turkey and 3Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria

Aim of the Study:

68Ga-DOTA-sst peptides are group of PET tracers that specifically bind to sstr that over-expressed on Neuroendocrine (NET) cells. Among them 68Ga-DOTA-NOC is a first compound for PET imaging with high affinity for sst2 and sst5. The aim of this study was to compare early and late image quality of 68Ga-DOTA-NOC in sstr positive organ and tumor by using SUVmax.

Materials and Methods:

Eleven patients (F/M: 5/6, mean age 54.72±15.33) with suspicious of NET were injected with 148±45 MBq 68Ga-DOTA-NOC. 30-60-90 minutes after injection of radiopeptides whole body PET/CT images were obtained. Images were evaluated visually and SUVmax values obtained in different time points from the pituitary, salivary gland,liver, spleen, adrenal glands, lesions were compared.

Results:

The late image quality of 68Ga-DOTA-NOC was not different than that of early 68Ga-DOTA-NOC and it did not provide additional informations according to lesion numbers and localisation. There was not significiant differences (P>0.05) in the SUV maxvalues of pituitary, salivary gland,liver, spleen, adrenal glands, lesions in between time period.

Summary:

68Ga-DOTA-NOC PET/CT can be used in the diagnosis and follow-up of NET patients after 30-90 min injection of radiopeptides.

Acknowledgments

This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number 3264.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-050: SUV of 68Ga-DOTATOC in Metastatic NET Lesions Varies with the Localisation of Primary Tumor Site

S.G. Kaeshammer1, M. Miederer1, C. Fottner2, M. Weber2, M. Schreckenberger1

1Department of Nuclear Medicine, University Medical Center, Mainz, Germany; 2Department of Endocrinology, University Medical Center, Mainz, Germany

Aim of the Study:

In patients with neuroendocrine tumors (NET) 68Ga-DOTATOC-PET/CT is an important tool for tumor-detection and follow-up. Somatostatin receptor expression is a key biologic parameter that correlates with standard uptake values (SUV). Somatostatin receptor expression may vary between different tumor entities as well as between the primary tumor and its metastases. Yet few trials have so far aimed to compare SUV in primary NET and NET metastases. We present a retrospective analysis of SUV ranges in NET and their metastases.

Materials and Methods:

Ga68-DOTATOC-PET/CT-Scans of 117 Patients with metastasised NET of the small bowel (39%), pancreas (24%), lung (9%) or other primary (28%) were included. We compared SUVmax in primary pancreatic (n=26) and bowel NET (n=17) and in a total of 133 metastases (45% liver, 39% lymph node and 18% bone metastases).

Results:

Median SUVmax in primary pancreatic NET (23.1; n=26) was higher than in bowel NET (9.5; n=17; P=0.008). SUVmax in primary lung NET was 27.6 (n=4). Metastases of pancreatic NET showed a tendency to higher SUVmax values (22.9; n=29) than metastases of bowel NET (15.6; n=72; P=0.081). In bowel NET liver metastases (20.9; n=29) showed higher SUVmax than bone (9.9; n=9) and lymph node (9.9; n=27) metastases (P=0.027 and P=0.007 respectively). In pancreatic NET a tendency to higher SUVmax was found in liver metastases (24.9; n=14) when compared to bone metastases (12.6; n=6) and lymph node metastases (14.7; n=6).

Summary:

In our study primary pancreatic NET showed significantly higher uptake than primary bowel NET. Primary lung NET showed the highest uptake values but the number of available cases (n=4) was insufficient for statistical analysis. NET metastases in the liver showed generaly higher uptake than NET metastases in the bone and lymph nodes, possibly indicating a slightly different biology.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-051: Immunhistochemical Expression of Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors using IRS- and Her2-scoring Scheme

Kämmerer, Daniel, L. Peter, A. Lupp, S. Schulz, J. Sänger, V. Prasad, M. Hommann, R.P. Baum

Zentralklinik, Bad Berka, Germany

Introduction:

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are known for an overexpression of somatostatin receptors (SSTR). This finding has already gained importance in diagnostics and therapy of NET.

Aims:

This study aims to achieve an immunhistochemical quantification of all 5 SSTR-subtypes and an evaluation of an implementable scoring system (Her2/IRS).

Material and Methods:

In 34 patients with GEP-NET 44 different tumor tissues were immunhistochemically analysed using polyclonal antibodies for SSTR1 and 3-5 and the monoclonal antibody UMB-1 for SSTR2A. SSTR expression was quantitatively evaluated according to HER2-score and IRS, correlated among each other and individually with clinical/ histopathological parameters.

Results:

According to IRS, the expression of SSTR3 dominated with 88.6%, followed by SSTR2A (86.4%), SSTR4, 1 and 5 (50-45%). IRS showed 16 different expression patterns (HER2 22), the dominating pattern being positive for 2A and 3 and positive for 1-3 and 5. SSTR1 and 4, 1 and 5 and 4 and 5 correlated significantly. IRS was found to be superior to HER2.

Conclusion:

Immunhistochemistry revealed heterogeneous expression patterns. SSTR2A and 3 were highly expressed, demonstrating the importance of SSTR for diagnostics and therapy. High incidences for SSTR3 and 4 give reason to think about present therapeutic principals, which are primarily concentrated on SSTR2A. IRS was suggested for a routinely diagnostic

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-052: Peptide Receptor Radionuclide Therapy with 177Lu Labeled Somatostatin analogues DOTATATE and DOTATOC - Contrasting Renal Dosimetry in the Same Patient

Christiane Schuchardt, Harshad Kulkarni, Vikas Prasad, Richard P. Baum

Department of PET/CT and Center for Nuclear Medicine, Zentralklinik Bad Berka, Germany

Aim:

Since kidneys are the dose-limiting organs in Peptide Receptor Radionuclide Therapy (PRRNT), renal dosimetry is crucial to avoid/minimize renal toxicity. 177Lu (beta and gamma emitter) is a common radioisotope used for PRRNT, a major advantage being the possibility of performing dosimetry. DOTATATE and DOTATOC are the two most commonly somatostatin analogues for PRRNT. The aim of this study was to compare the renal uptake, residence time and the resulting renal dose between 177Lu-DOTATATE and 177Lu-DOTATOC, when delivered during consecutive cycles of PRRNT in the same patient, and correlate these parameters with the effect on renal function after therapy.

Materials and Methods:

Twenty-two patients with metastatic neuroendocrine tumors (12 male and 10 female; age 45.3 - 75.5 y) underwent treatment with 177Lu-DOTATATE (5.0 - 9.5 GBq) and 177Lu-DOTATOC (5.5 - 8.5 GBq) 10-14 months apart from each other. The time-dependent kidney activity was determined based on conjugated planar whole-body scans acquired 0.5h, 3h, 20h, 44h and 68h post injection and dosimetric calculations (MIRD scheme) were performed using OLINDA software. The patients were followed up with serum creatinine, tubular extraction rate (TER) using 99mTc-MAG3 scans and glomerular filtration rate (GFR) using 99mTc-DTPA before and after therapy for 3 - 8 months. Age, hypertension and diabetes were associated risk factors for renal toxicity, which were taken into account. Five of the 22 patients had elevated serum creatinine before PRRT, 3 of whom had a history of hypertension, 1 had diabetes mellitus and 1 with age >65 years.

Results:

The uptake, residence time and the mean absorbed dose to the kidney per unit administered activity were slightly but significantly higher for DOTATATE (actual absorbed dose between 1.9 - 9.2 Gy) as compared to DOTATOC (dose between 2.3 - 7.8 Gy) in 19 out of the 22 patients (86%)(P<0.05). The tumor to kidney ratio was higher for DOTATOC in 23 out of 43 (53%) lesions analyzed; however this was not statistically significant. There were no statistically significant changes in serum creatinine, TER or GFR pre- and post-therapy with either DOTATATE or DOTATOC.

Summary:

177Lu-DOTATATE and 177Lu-DOTATOC are safe radiopharmaceuticals concerning renal toxicity. Both appear to be equivalent with respect to the tumor to kidney ratio. The dose to the kidney with 177Lu labeled peptides is significantly lower than that with 90Y labeled DOTATATE/-TOC, which corresponds to a lower renal toxicity. 177Lu-DOTATOC gives a slightly but significantly lower renal dose. Finally, this study underlines the importance of clinical screening for risk factors of chronic renal disease.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-053: Comparison of Receptor Expression in Normal Spleen and Splenosis by Somatostatin Receptor PET/CT and Correlation with Immunohistochemistry

Vikas Prasad, Harshad Kulkarni, Daniel Kaemmerer, Jörg Sänger, Richard P. Baum

Zentralklinik, Bad Berka, Germany

Aim:

Splenosis is a rare condition involving autotransplantation of normal splenic tissue in the peritoneal cavity after trauma to the spleen (splenectomy or abdominal injury). It has histological features different from that of normal spleen. It is well known that the spleen exhibits a very high uptake of somatostatin receptor (SSTR) analogues; however, the mechanism of this phenomenon has not been clearly elucidated. The aim of our study was to compare the expression of somatostatin receptors in splenosis and normal spleen by somatostatin receptor PET/CT (SMS-R PET/CT) using 68Ga-DOTATOC, and to correlate and ascertain the histological basis of the SSTR expression by immunohistochemical analysis of the spleen cells.

Materials and Methods:

10 patients with known neuroendocrine neoplasm involving the tail of the pancreas first underwent SMS-R PET/CT for staging. SUV maxof the spleen was documented. Accessory spleens were ruled out on pre-therapy CT/MRI. Then, left pancreatectomy and splenectomy was performed. 10 paraffin blocs from 3 of the spleen specimens were analysed by histology and immunohistochemistry using monoclonal antibodies to SSTR 2A, CD20 and CD3. Post splenectomy CT and MRI performed for follow up after 3 - 6 months, showed evidence of splenosis in the left hypochondrium in all of these patients. SUV maxof splenosis in each patient was noted on follow up SMS-R PET/CT using 68Ga-DOTATOC.

Results:

The SUVmax (mean±SD) of the splenosis was 10.5±4.3 and that of normal spleen was 28.8±12.5 (around 3 times that of splenosis). T-lymphocytes (expressing CD3) and B-lymphocytes (expressing CD20) were found scattered in the red pulp of the spleen, but more clustered in the white pulp (Malpighian corpuscles) with B-lymphocytes at the centre and T-lymphocytes at the periphery. The staining for SSTR 2A was highly concentrated in the B- and T- lymphocytes in the white pulp.

Conclusion:

In this study, splenosis was found to have extremely low somatostatin receptor expression on SMS-R PET/CT as compared to the normal spleen. SSTR 2A is strongly expressed by T- and B- lymphocytes in the white pulp of the spleen resulting in a high splenic uptake on somatostatin receptor PET/CT using 68Ga-DOTATOC (which also has a high affinity to SSTR 2A). The findings in our study are concordant with the fact that splenosis has poorly formed or deficient white pulp with normal-appearing red pulp, as described in previous histological studies.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-054: Is there a Correlation Between Peptide Receptor Radionuclide Therapy Associated Hematological Toxicity and Spleen Dose?

Christiane Schuchardt, Harshad Kulkarni, Vikas Prasad, Richard P. Baum

Zentralklinik, Bad Berka, Germany

Aim:

The spleen receives the highest radiation dose during Peptide Receptor Radionuclide Therapy (PRRNT). This is due to high somatostatin receptor expression by T- and B-lymphocytes in the white pulp of the spleen. Even though the spleen is not the site of formation of blood cells, it serves as a reservoir of erythrocytes and platelets, to be made available in the event of an emergency like hemorrhagic shock, and of leucocytes particularly undifferentiated monocytes, which are mobilized and deployed at the sites of inflammation. There have been no previous studies examining the effect of high radiation dose to the spleen and therefore to the pooled blood cells during PRRNT.The aim of this study was to correlate between the radiation dose to the spleen and the effect on the blood cell count after PRRNT.

Materials and Methods:

The study included 53 patients having undergone a single cycle of PRRNT with 3.8 - 8.5 GBq of 177Lu-DOTATATE or DOTATOC. The time-dependent spleen activity was determined based on conjugated planar whole-body scans acquired 0.5h, 3h, 20h, 44h and 68h post injection and dosimetry calculations (MIRD scheme) were performed using OLINDA software. 11 patients who had undergone splenectomy before PRRNT were treated with 4.7 - 7.6 GBq of 177Lu DOTATATE or DOTATOC and were selected as controls. The patients in study and control groups were selected after excluding past history of chemotherapy. The RBC, WBC (total and differential) and platelet counts before and after each cycle of PRRNT were documented. Non-parametric sign rank tests were used to compare the post-therapy changes in blood cell counts in the study group and splenectomy group (control).

Results:

The median dose to the spleen in the study group was 6.34 Gy (2.32 - 20.06). There was no significant difference in the post-therapy changes in the blood cell counts (RBC, WBC or platelets) between the study group and the control group. Mild hematological toxicity was found in 7 of the 53 (13.2%) patients in the study group and all of these patients presented with mild erythrocytopenia. However, there was no correlation between the incidence and grade of hematological toxicity, and the dose to the spleen. In the control group, 1 out of the 11 patients (9.1%) had mild erythrocytopenia post PRRNT.

Conclusion:

PRRNT with 177Lu-labeled peptides is safe and has minor adverse hematological effects, mostly mild erythrocytopenia. However, this is most likely due to the radiation dose to the whole body (including bone marrow) and most probably unrelated to the radiation dose to the spleen.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-055: 5-year Follow-up of Renal Function of Neuroendocrine Tumor Patients Treated with 5 or More Cycles of Peptide Receptor Radionuclide Therapy

V. Prasad, D. Hoersch, C. Zachert, R.P. Baum

Zentralklinik, Bad Berka, Germany

Aim:

Nephrotoxicity is one of the primary concerns in peptide receptor radionuclide therapy (PRRNT), where loss of renal function may become apparent only after many years. The aim of this study was to analyze the time course of the Tubular Extraction Rate (TER) and Glomerular Filtration Rate (GFR) in patients with metastasized progressive neuroendocrine tumors treated with at least 5 cycles of PRRNT and followed up for a minimum duration of 5 years.

Materials and Methods:

This analyses consisted of 32 patients treated with atleast 5 cycles of PRRNT (range 5-8) with Y-90 (n=2, each patient treated with 7 cycles) or a combination of Y-90 and Lu-177 (n=30) labeled Somatostatin-Receptor analogues (DOTATAE / DOTATOC). The total cumulative administered radioactivity ranged from 16.5 to 41 GBq. Each patient was received amino-acid infusion and some of them received gelofusal according to our standard nephroprotection regime. In addition all the patients were well hydrated prior to therapy and were trained to maintained adequate life-long hydration. Assessment of renal function was carried out by calculating tubular extraction rate using 99mTc- MAG3 (plasma clearance based on Bubeck's formula) and GFR was measured using single sample plasma clearance of Tc-99m DTPA.

Results:

None of the patients had Grade 3 or higher toxicity. Nine patients (28%) had grade 1 while 5/32 (16%) patient showed grade 2 toxicity. Seven patients showed fall in renal function of more than 20%. One patient showing TER fall of 51% had recurrent urinary tract infection. Arterial hypertension, long standing diabetes mellitus, carcinoid heart disease, tumor induced hypercalcemia and hepatomegaly were found to be co-existing risk factors.

Conclusion:

PRRNT under Bad Berka protocol using a combination of Y-90 and Lu-177 DOTATATE/DOTATOC does not lead to any severe nephrotoxicity. As previously reported and mentioned above there are certain risk factors which contribute to mild nephrotoxicity of PRRNT. Appropriate life long hydration should be recommended to all patients to avoid chronic loss of renal function post PRRNT.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-056: Comparison of Kidney Uptake Values for 68Ga-DOTATATE and 111In-DTPA-Octreotide at Different Time Points

Kwadwo Antwi, C. Zhou1, H. Reber, H.G. Buchholz, C. Fottner, M. Miederer

Klinik und Poliklinik für Nuklearmedizin, Universitätsmedizin Mainz. Langenbeckstr. 1, 55131 Mainz, Germany

Aim of the Study:

In Somatostatin receptor targeted therapy with the somatostatin analogue 177Lu -DOTATATE (DOTA-Tyr³-Octreotat) for treatment of patients with neuroendocrine tumors renal toxicity occurs and therefore accurate pretherapeutic dosimetry is advisable for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for the kidney based on 111In-DTPA-octreotide (Indium-111 DTPA-D-Phe1-octreotide, OctreoScan) Dosimetry was compared with uptake values derived from the positron emission tomography (PET) tracer 68Ga- DOTATATE. The aim of our study was to compare the uptake value of 68Ga-DOTATATE PET as a possible surrogate marker for Lutetium-177-DOTATATE Dosimetry.

Materials and Methods:

Six patients with metastatic carcinoid tumors who previously received 111In-DTPA-octreotide Dosimetry were investigated. Quantitative PET/CT studies for the same patients with 68Ga-DOTATATE were recorded 1 and 3h post-injection to measure the uptake kinetic in kidneys. On the basis of the computed tomography Volumes of interest were drawn over the kidneys. These volumes of interests were used to measure 68Ga-DOTATATE uptake. The kinetics of 111In-DTPA-octreotide were used to calculate the radiation doses for 177Lu -DOTATATE.

Results:

The mean uptake value for the kidneys at the earliest time point (0,1h) for the In-111-Octreoscan where 2,51±0,73% of injected dose and for later time point (4h) 2,01±0,71. The mean uptake value at the earliest time point (1 h) for the 68Ga- DOTATATE where 1,67±0,34 and for later time point (4h) 1,9±0,56. When comparing the mean uptake values via t-test, no significant differences were found (P=0,14 for early time point and±=0,87 for late time point).

Summary:

Exact uptake values derived from PET/CT with 68Ga- DOTATATE are comparable to planar Uptake value derived from 111In-DTPA-octreotide (Octreoscan). For dosimetry calculation more PET/CT time points and possibly later time points might be necessary.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-057: Dosimetry in Peptide Receptor Radionuclide therapy: Comparative Results using Lu-177 DOTA-TATE, DOTA-NOC und DOTA-TOC

Christiane Schuchardt, Harshad Kulkarni, Richard P. Baum

Department of Nuclear Medicine, Center for PET/CT, Robert-Koch-Allee 9, 99437 Bad Berka, Germany

Aim:

Peptide receptor radionuclide therapy with radiolabelled octreotide analogues is effective in patients with somatostatin receptor (sstr) positive tumors. The peptide DOTA-NOC exhibits in vitro the highest affinity to sstr subtypes 3 and 5 and a high affinity to sstr 2. We analyzed the in vivo behavior of the Lu-177 labelled peptides DOTA-TATE, DOTA-NOC and DOTA-TOC by measuring organ- and tumor kinetics and by dosimetric calculations.

Materials and Methods:

We examined 223 patients with metastasized neuroendocrine tumors with high somatostatin expression as verified by Ga-68 DOTA-NOC PET/CT. 173 patients received 5.7±1.1GBq Lu-177 DOTA-TATE, 10 patients were treated with 5.6±1.5 GBq Lu-177 DOTA-NOC and 41 patients were treated with 7.1±0.8 GBq Lu-177 DOTA-TOC. The time-dependent whole-body, organ and tumor activities were determined based on conjugated planar whole-body scintigraphies acquired 0.5h, 3h, 20h, 44h and 68h p.i. and dosimetric calculations (MIRD scheme) were performed using OLINDA software.

Results:

The highest uptake was found for DOTA-NOC (whole-body, kidneys and spleen), and the lowest for DOTA-TOC. Considering the nearly identical half-lives of the three peptides, higher whole-body and organ-doses were calculated for DOTA-NOC as compared to DOTA-TATE and DOTA-TOC (which exhibited the lowest organ doses). In tumor lesions, the uptake of the three somatostatin analogs was comparable at 20h p.i., but there were differences early after infusion (0.5h p.i.): DOTA-TATE initially increased to 0.07% until 20h p.i., where as DOTA-NOC and DOTA-TOC started immediately at 0.09%. All agents showed an exponential decrease thereafter. The mean absorbed doses to tumor lesions were comparable for all 3 peptides.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-058: Dosimetry in Internal Radiation Therapy: The Bad Berka Protocol

Christiane Schuchardt, Harshad Kulkarni, Richard P. Baum

Department of Nuclear Medicine, Center for PET/CT, Robert-Koch-Allee 9, 99437 Bad Berka, Germany

Aim:

Calculating the absorbed dose is important for the determination of risk and therapeutic benefit of internal radiation therapy. Optimal dose estimations require time-consuming and sophisticated methods, which are difficult due to practical reasons. To make dosimetry available for each of the patients, we developed a specific dosimetry procedure used in daily clinical routine.

Materials and Methods:

Dosimetry has been performed according to the MIRD-scheme and adapted to the special conditions at our department: Conjugated planar whole-body scintigraphies at 0.5h, 3h, 24h, 48h and 72h p.i. are analyzed by regions of interest (ROIs) with Hermes Whole Body Display and the time-dependent whole-body, organ and tumor activities, including geometric mean and background correction, are determined with Microsoft EXCEL. The cumulated activity (residence time) is calculated using the software ORIGIN PRO 7G and a mono- or biexponential fit of the time-activity curves. In the last step, mean absorbed organ and tumor doses are estimated using the software OLINDAEXM.

Results:

We found a compromise between the calculation model (given by the MIRD-scheme) and practical conditions. It has ensured dose estimation in daily clinical routine with a reasonable effort and within acceptable time. In consequence, the dosimetry method developed for Bad Berka allows each of our patients to undergo dosimetry after therapy using Lu-177 labeled peptides (peptide receptor radionuclide therapy, PRRNT). Additionally, the Bad Berka Dosimetry approach can be used for any internal radiotherapy using a gamma-emitting radionuclide.

Conclusions:

The Bad Berka Dosimetry method is a practicable dosimetric approach, which can be used in daily clinical routine. It not only helps in identifying patients who would benefit most from the treatment, but also those with unfavourable dosimetry. Additionally, the analysis of dosimetric data from PRRNT could help in predicting possible toxicity or side effects.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-059: Lu-177 BPAMD for Treatment of Skeletal Metastases in Prostate Cancer: First Dosimetric Results

Christiane Schuchardt, Harshad Kulkarni, Frank Rösch, Richard P. Baum

Department of nuclear medicine / Center for PET, Robert-Koch-Allee 9, 99437 Bad Berka, Germany

Aim:

Lu-177 BPAMD (4-{[bis-(phosphonomethyl)) carbamoyl] methyl}-7, 10-bis (carboxymethyl)-1, 4, 7, 10-tetraazacyclododec-1-yl acetic acid) is a promising new agent for the treatment of skeletal metastases in prostate cancer. The aim of our study was to determine the organ and tumor kinetics and to estimate the mean absorbed dose to normal organs and tumor lesions.

Materials and Methods:

5 patients (aged 68.5±3.8 years) suffering from carcinoma of prostate with skeletal metastases were treated with activities of 3.5-6.2GBq Lu-177 BPAMD. One patient received 3 cycles of therapy. In total, 7 dosimetric studies were included in the analysis. On the basis of conjugated planar whole-body scintigraphies 0.5h, 3h, 24h, 48h and 72h p.i. the time-dependent whole-body, organ and tumor activities were determined and dosimetric calculations performed according to the MIRD scheme using OLINDA/EXM software. To describe the kinetics we used the following parameters: mean half-life (hours) and uptake (%IA, fraction of injected activity), which were calculated using the fit of the time-dependent activity curve to a mono- or bi-exponential function. Blood samples were drawn in 4 patients to estimate the absorbed dose to the red marrow.

Results:

The whole body (WB) uptake showed a bi-exponential decrease, the second half-life was 64±20h and varied from 20 to 50% IA at 20h p.i. The resulting mean absorbed WB dose was 0.08±0.04mGy/MBq. A rapid decline was found for the renal uptake, followed by a mono-exponential function after 20h p.i. and a half-life of 49±18h. The maximum kidney uptake was 4%IA. The uptake of the bone lesions showed a first increase until 3h p.i. followed by a slow decrease with a very long half-life of 58-160h (identical to the physical half-life of Lu-177). The blood kinetics were fitted to a tri-exponential function with low variation: half-life 1: 4-8min; half-life 2: 55-88h and half-life 3: 15-23h. The following organ absorbed doses were calculated: whole body: 0.04-0.13mGy/MBq, kidneys: 0.11-0.63mGy/MBq; skeletal metastases: 2.4-209mGy/MBq. The resulting dose to the red marrow was 0.04-0.1mGy/MBq.

We found a high inter-patient variability when comparing the dosimetric results of all patients. Contrary, the intra-patient variability was very low concerning one patient receiving 3 cycles of therapy

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-060: Radiation Exposue of the Personnel During Radiolabelling of 68Ga-DOTATOC

J. Rose, V. Nataf, A. Prignon, F. Montravers, J.N. Talbot

Tenon Hospital, 4, rue de la Chine 75020 Paris, France

Objective:

68Ga-DOTATOC, a clinical experimental drug used for the diagnosis of neuroendocrin tumor, has been prepared by the radiopharmacist in the Nuclear medicine department at Tenon Hospital for 2 years. 68Ga is available from a 68Ge/68Ga generator-system (cyclotron Co., Ltd., Obninsk, Russia and pharmaceutically certified by Iason GmbH) and the radiolabelling is performed by a semi-automated module (developed by Iason GmbH), which is controlled by software running on a laptop. The aim of this study is to evaluate the operator's total body and fingers irradiation during the DOTATOC radiolabelling and the quality controls processes.

Materials and Methods:

The radiolabelling of DOTATOC by 68Ga is performed inside a hot cell suited for high energy radiations. Several steps are needed to obtain a product suitable for human use: disinfection and cleaning of the hot cell and the module, radiolabelling and quality controls, which are performed outside the hot cell. In order to determine irradiation during these steps, the preparator wore an active dosimeter on the chest and 10 thermoluminescent dosimeters mounted on rings around the fingers (base of the thumb, base and extremity of the index and middle finger of each hand). The study was performed with 5 radiolabelling. The mean activity manipulated is 280 MBq of 68Ga-DOTATOC.

Results:

Results from the active dosimeter showed no increase as compared to natural radiation exposure (3μSv per radiolabelling). Conversely, fingers were significantly irradiated especially at the base and extremity of the left index (85 to 160 μSv).

Conclusion:

This study shows that radiolabelling and quality controls of 68Ga-DOTATOC are performed with safe procedures as relates to user irradiation. We estimate to 140 the number of 68Ga-DOTATOC PET examinations performed per year, amounting to a maximal exposure of 22 mSv for the preparator's hands, which is largely lower than annual legal dose limits.

World J Nucl Med. 2011 Jan-Jun;10(1):98–107.

P-061: Radiation Protection in Peptide Receptor Radiation Therapy-A Six Years Experience

Stefan Senftleben, Arndt Rimpler, Marcel Wieditz, Richard P. Baum

Zentralklinik Bad Berka GmbH, Klinik für Nuklearmedizin/PET-Zentrum. Robert-Koch-Allee 9, D-99437 Bad Berka, Germany

Introduction:

Peptide Receptor Radiation Therapy (PRRT) has become an important treatment option in the therapy of neuroendocrine tumors. From Jan. 2004 to May 2010 we performed 1084 therapies with Y-90 and 1338 therapies with Lu-177 labelled peptides. The applied activities were in the range of 1.5 to 6 GBq Y-90 and 3 to 10 GBq Lu-177 per patient.Thus, high activities had to be handled by medical and technical staff. High radiation exposure especially to the hands and the risk of contamination were the challenges for the radiation protection.Our poster describes the development of standard operational procedures as well as radiation protection methods and equipment due to an increasing number of applications over the years.

Materials and Methods:

Measurements of the dose rate for beta and gamma radiation had been performed with different dose rate meters. Our personnel routinely wears official ring TL-dosemeter for beta/photon radiation. In collaboration with the Bundesamt für Strahlenschutz, the radiation exposure of the skin on the fingers has been investigated with TLD tapes which were fixed to various positions on both hands. The doses measured with ring and tape TL-detectors were compared in order to find the most appropriate position of the ring dosemeter in routine monitoring. Additionally, the effect of modifications of the application equipment (infusion lines, shielding of infusion pump) on the staff exposure has been investigated.

Results:

The occupational radiation exposure of the staff is dominated by the skin dose on fingers rather than whole body exposures. The individual doses vary over a wide range and can exceed the annual limit of 500 mSv if safety rules are neglected. The labelling of the radiopharmaceuticals is performed in a special Beta-lab under high protection standards. The radiation exposure of radiochemistry staff involved in these procedures was lower than the exposure of the nurses doing the application to the patients.

As an example, Table 1 shows the results of routine skin dose monitoring of 3 nurses (A,B,C) involved in PRRT applications. A good training of the application procedure and improvements on equipment and handling helped to reduce the annual skin dose in spite of increasing numbers of applications.

Table 1.

Skin dose per year, dose values in mSv

graphic file with name WJNM-10-98-g001.jpg

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Between 2004 and 2009 we observed 1 case of contamination because of a bad connection line. The shielded application cart had been decontaminated properly. The nurse who decontaminated the cart got a whole body counter measurement to exclude an incorporation of radionuclides.

Conclusions:

The handling of high beta activities can be performed safely if personnel follows safety rules accurately and reliable. New staff has to be trained very well. They should take care to wear the finger ring detectors properly and check for contaminations of themselves or of the equipment frequently. The base or better the second phalanx of the index-finger of the non-dominant hand was found to be the most suitable location for wearing a ring dosemeter. SOP’s and technical equipment should be improved continuously.

Articles from World Journal of Nuclear Medicine are provided here courtesy of Thieme Medical Publishers

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