Oral Presentation

. 2017 Dec;32(Suppl 1):S2–S32.

Oral Presentation

PMCID: PMC5770897

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Clinical Nuclear Medicine: OP 1:233530: Diuretic renogram for assessment of postpyeloplasty outcome: Revisiting critical parameters

A S Rahul ¹, Shwetal Pawar ¹, Mangala Ghorpade ¹, Suruchi Shetye ¹

Background: Pelvi-ureteric junction obstruction (PUJO) is the most common form of obstruction in the upper urinary tract. Surgical repair is indicated by significantly impaired renal drainage or progressive deterioration of renal function. The purpose of the study was to assess find out which is the better parameter to assess response to pyeloplasty.

Materials and Methods: This was a retrospective study on 52 children who underwent pyeloplasty for PUJO, out of which 16 children were <5 years old and 36 children were >5 years old. Technetium-99m diethylene-triamine-pentaacetate acid (mean activity 2 mCi) or ethylenedicysteine scan (mean activity 1.5 mCi) were done before and at least 3 months after the pyeloplasty using F+0 protocol. Differential function, curve pattern, cortical peaking, T½, and corticocalyceal transit (visual) were evaluated on both studies and significance level was assessed.

Results: In the >5 years of age group, 8 (22.2%) children showed improvement in cortical function, 8 (22.2%) children showed improvement in cortical peaking time, 6 (16.7%) children showed improvement in time to half peak, and 19 (52.8%) children showed improvement in excretion of radiotracer; failure rate of the surgery is 22.2%. In the <5 years of age group, 4 (25%) children showed improvement in cortical function, 6 (37.5%) children showed improvement in cortical peaking time, 4 (25%) children showed improvement in time to half peak, and 11 (68.75%) children showed improvement in excretion of radiotracer; failure rate of the surgery is 12.5%. Further study in a subgroup of 36 patients whose age were >5 years at the time of surgery, the result shows statistically significant improvement in cortical function as the P value is 0.04 and the Wilcoxon signed-rank test score is −2.058.

Highlights of Research: Differential cortical function in >5 years age was the significant factor to assess the pyeloplasty outcome which is an additional finding to the existing literature.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 2:230315: Retrospective analysis of technetium-99m diethylene-triamine-pentaacetate acid scan findings in prospective kidney donors: Experience from a single tertiary care center in India

E Ram Kumar ¹, Ankur Pruthi ¹, Promila Pankaj ¹, Ritu Verma ¹, Ethel S Belho ¹, Harsh Mahajan ¹

Rationale: Glomerular filtration rate (GFR) estimation is the primary investigation required for selecting “prospective kidney donors” before renal transplantation. GFR estimation by Gate's protocol using Gamma camera is one of the most common methods used for this purpose. The aim of this research was to study the epidemiological, laboratory, and imaging profile of the prospective kidney donors in our population.

Methodology: A total of 1022 prospective kidney donors (330 males, 692 females; mean age 48.2 ± 11.9 years; range 18–78 years) who underwent diethylene-triamine-pentaacetate acid scan for GFR estimation in our department between 2014 and 2017 were retrospectively analyzed. GFR was estimated using the Gate's method. GFR >70 ml/min was considered acceptable for kidney donation. Various parameters such as age, sex, serum creatinine, total GFR, and differential function were recorded. The data were analyzed using appropriate statistical methods.

Key Results: Majority of the prospective renal donors were in the age group of 40–59 years (59% among females and 52% among males). 67.7% of the total prospective renal donors were females. Mean GFR recorded for total population was 81.7 ± 16.5 ml/min. There was no significant difference in mean GFR between males and females (P > 0.05). 19.4% of the total study population had GFR <70 ml/min. The mean age in this subgroup was 57.87 ± 10.23 years and mean serum creatinine was 0.80 mg/ml. Majority of donors with GFR <70 ml/min were in the age group of 50–69 years (73.53% among females and 64.52% among males).

Research Highlights: Majority of the prospective renal donors belonged to the age group of 40–59 years and were females. There was no significant difference in mean GFR between both sexes. Donors belonging to younger age groups have a higher chance of acceptance for renal donation.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 3:112112: Renal and hematological toxicity in patients undergoing Lu-¹⁷⁷-DOTATATE capecitabine therapy for neuroendocrine tumors

Ajay Mohan ¹, Ashwani Sood ¹, Priya Bhusari ¹, Jaya Shukla ¹, Bhagwant Rai Mittal ¹

Introduction: Neuroendocrine tumors (NETs) have neuro-endocrinal origin. There are many types of NETs and most of them express the somatostatin receptors 2 and 5. Positron emission tomography imaging using Ga-⁶⁸-somatostatin analogs is routinely used to assess the distribution, spread of disease, and prognostication and indicate the patient's suitability for peptide receptor radionuclide therapy (PRRT). PRRT is used in patients with metastatic/inoperable disease using ¹⁷⁷Lu-labeled somatostatin analogs and capecitabine. The risk of toxicity associated with this treatment is there. The kidneys are the critical organ in ¹⁷⁷Lu-DOTATATE therapy because the uptake is mediated by the endocytic receptor megalin in the proximal tubuli of the nephron followed by hematological toxicity. The aim of this study is to assess the renal and hematologicaltoxicity in patients undergoing PRRT with ¹⁷⁷Lu-DOTATATE along with capacetabine.

Methods: Sixty-one patients underwent NETs therapy (variable cycles of therapy) with Lu¹⁷⁷-DOTATATE (200 mCi per cycle) after fulfilling the eligibility criteria. Amino acid infusion was done along with administration of Lu-¹⁷⁷-DOTATATE for nephroprotection. A posttherapy scan was performed 24 h postadministration of therapy dose. The patients were followed-up with determination of renal function including glomerular filtration rate evaluation, liver function, and complete hemogram on 3^rd, 6^th, and 9^th week after each cycle of Lu-177-DOTATATE therapy.

Results: Evaluation of renal function at 3^th, 6^th, and 9^th week intervals did not show significant reduction in renal parameters. Furthermore, the blood profiles at these time intervals did not show significant reduction in cell counts and hemoglobin content. In few patients, a significant increase in the serum creatinine level and mild drop in the platelet count was observed during the therapy.

Conclusion: PRRT with Lu¹⁷⁷-DOTATATE in NETs with amino acid infusion is an effective and safe treatment with transient toxicity in few of patients of the study group.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 4:145312: Role of texture parameters evaluated from baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography images in prediction of treatment response of nonsmall cell lung cancer

Akshima Sharma ¹, Anil Kumar Pandey ¹, Anant Mohan ¹, Ashu Seith Bhalla ², V Sreenivas ³, Mehar Chand Sharma ⁴, Chandan J Das ², Sanjay Thulkar ², Chetan D Patel ¹, C S Bal ¹, Anshul Sharma ¹, Rakesh Kumar ¹

Objective: A quantitative parameter of baseline 18F-fluorodeoxyglucose F-18 positron emission tomography/computed tomography (F-18 FDG PET/CT) image that can predict the chemotherapy treatment response is required so that the toxic effect of chemotherapy can be avoided in patients. In this study, we have evaluated the role of texture analysis of the baseline F-18 FDG PET/CT images of nonsmall cell lung cancer (NSCLC) in prediction of response.

Methodology: Twenty-five patients (M/F: 18/7) with biopsy-proven NSCLC and mean age 58.16 ± 10.88 years planned to undergo platinum-based chemotherapy were enrolled. They underwent a pretreatment F-18 FDG PET/CT after injecting 0.14–0.21 mCi/kg of F-18 FDG intravenously. Patients were divided into two response groups on the basis of RECIST 1.1 criteria, i.e., responders and nonresponders. Metabolic parameters (i.e., tumor-to-background ratio, maximum standardized uptake value [SUVmax], average standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis [TLG], whole-body MTV, and whole-body TLG) were evaluated using three-dimensional isocontour regions of interest with threshold 2.5 SUVmax. The displayed PET/CT images were exported in JPEG format to perform texture analysis using in-house developed program written in MATLAB R2013b. Thirteen textural features based on gray-level co-occurrence matrix (16 bins, 0° direction, 1 pixel distance) were calculated. Association of parameters with two response groups was determined by Mann–Whitney U-test and receiver characteristic curve (ROC) analysis. P < 0.05 was considered statistically significant.

Results: Out of 13 parameters the median values of five texture parameters, i.e., energy, entropy, difference variance (DV), inverse difference moment (IDM), and sum entropy (SE) were significantly different among responders (0.170, 2.710, 0.0369, 0.863, and 2.3891, respectively) and nonresponders (0.073, 3.294, 0.0304, 0.808, and 2.8383, respectively) with P< 0.05. The area under the ROC curve (AUROC) for energy, entropy, IDM, and DV is 0.76 with threshold 0.09, 2.85, 0.834, and 0.033, respectively. AUROC for SE is 0.74 with threshold 2.57. The metabolic parameters of baseline F-18 FDG PET/CT were not able to predict response.

Conclusion: The texture parameters evaluated from baseline F-18 FDG PET/CT images can predict treatment response in NSCLC.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 5:153841: ^99mTc sulfur colloid single-photon emission computed tomography for quantitative functional liver assessment in patients with decompensated cirrhosis: Correlation with indocyanine green and liver severity scores

Amritjyot Kaur ¹, Virendra Singh ¹, Anish Bhattacharya ¹, Baljinder Singh ¹

Rationale: Quantitative functional capacity of liver is estimated with indocyanine green (ICG) clearance which is cumbersome. ^99mTc sulfur colloid single-photon emission computed tomography (SPECT) scan is assessed for quantitative liver function in patients with decompensated cirrhosis and correlated with ICG clearance and disease severity scores.

Methods: Threshold value and regression line for SPECT quantitation were obtained using serial phantom images with varying volume and concentration. Seventy-three patients underwent ^99mTc sulfur colloid SPECT scan. The data obtained were reconstructed using three-dimensional volumetric analysis software to calculate the quantitative liver uptake (QLU), % injected dose/mL of liver, and liver volume (LV). Forty-six patients also underwent ICG clearance test after intravenous administration of ICG (0.4 mg/kg) followed by blood sample collection at 15 min to calculate ICG (R15).

Results: The best threshold value was estimated to be 38. The QLU values exhibited a significant correlation with Child-Turcotte-Pugh (CTP) (r = −0.69, P < 0.001), Model for End-Stage Liver Disease (MELD) score (r = −0.55, P = 0.000), and ICG (R15) (r = −0.51, P < 0.001). Likewise, ICG (R15) also showed a significant correlation with CTP (r = 0.76, P < 0.001) and MELD (r = 0.71, P < 0.001). On the other hand, a medium-level correlation was observed between LV and CTP (r = −0.56, P< 0.001) and MELD (r = −0.48, P < 0.001). In CTP A, LV was significantly increased (1129 ± 219), compared to CTP B (943 ± 259, P < 0.01) and CTP C (701 ± 156, P < 0.001). QLU for CTP A was also higher (36.44 ± 7.8) as compared to CTP B (25.34 ± 9.41) (P< 0.001) and CTP C (12.25 ± 4.77) (P < 0.001).

Conclusion: The study has shown quantitative SPECT of the liver as an additional, useful, noninvasive quantitative test for assessment of hepatic function and severity of disease in decompensated cirrhotic patients. However, it needs validation through larger cohort of patients.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 6:000042: Evaluation of liquid gastric emptying time from gastroesophageal reflux scan in children

Rakesh Joshi ¹, R Vishnukumar ¹, H Dhanapathi ¹, Nandin Pandit ¹, Madhusudhanan Ponnusamy ¹

Introduction: Gastroesophageal (GE) reflux scintigraphy can be used to assess liquid gastric emptying time in children which provides with additional gastric motility information. Assessing of liquid gastric emptying time in GE reflux scintigraphy is a feasible method and can be of clinical importance in providing additional gastric motility information.

Aim: (1) To estimate liquid phase gastric emptying time from GE reflux scan done in children who was referred to Department of Nuclear Medicine in suspicion of GE reflux disease. (2) To compare liquid gastric emptying time between GE reflux positive and negative groups.

Methods: This study was carried out retrospectively in 14 children (age: 2 months–4 years) who have undergone GE reflux scintigraphy between May 17 and August 17. It is done using technetium-99m-sulfur colloid/diethylene-triamine-pentaacetate acid (0.2 mCi–0.5 mCi) labeled milk (80 ml–150 ml) administered orally/through nasopharyngeal tube. The GE reflux study was carried out in dynamic/cine acquisition for 30 min (10 s/frame × 180 frames) in anterior view and subsequent processing was done. Data were collected and analyzed using SPSS. 21.0.

Results: Out of 14 patients, 10 were positive and four were negative. Median liquid gastric emptying time (T½) is 48 min with interquartile range (35.75–70). Median activity retained in the stomach was about 72% interquartile range (60–80). Among the reflux-positive group, mean T½ was 58, and among the reflux-negative group, mean T½ was 42 min. There was no statistically significant difference between mean gastric emptying time among GE reflux-positive and reflux-negative groups.

Conclusion: Median liquid gastric emptying time was 48 min. Median activity retained was 72%. There was no statistically significant difference between mean gastric emptying time among GE reflux positive and negative groups. By assessing of liquid gastric emptying time in GE, reflux scintigraphy is a feasible method and can be of clinical importance in providing additional gastric motility information.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 7:201332 : Low-dose remnant ablation in differentiated thyroid carcinoma: A single-center experience

M S Bharadwaj ¹, P A Meivel ¹, P Madhusudhanan ¹, H Dhanapathi ¹, Nandini Pandit ¹

Objective: This study is aimed to assess the effectiveness of low-dose remnant ablation with 30 mCi of I-131 in differentiated thyroid carcinoma patients.

Methods: Patients with differentiated thyroid carcinoma who underwent low-dose remnant ablation with 30 mCi of I-131 between 2014 and 2017 were analyzed retrospectively. Pretreatment andfirst follow-up radioiodine whole-body scans and serum thyroglobulin levels were compared.

Results: A total of 42 patients had undergone remnant ablation with 30 mCi of I-131 and had theirfirst follow-up data available. Median age was 35 and male to female ratio was 1:13. Histopathology reports of these patients were classical variant of papillary carcinoma of thyroid – 64%, follicular variant of papillary carcinoma of thyroid – 28%, minimally invasive follicular carcinoma – 5%, and papillary microcarcinoma – 3%. Complete resolution of remnant atfirst follow-up scan was seen in 50% of patients. Median serum thyroglobulin levels at pretreatment andfirst follow-up were 7.8 and 2.5, respectively.

Conclusion: Low-dose remnant ablation in differentiated thyroid carcinoma is an effective adjuvant therapy following surgery. Fifty percent of patients were iodine scan negative in thefirst follow-up with complete resolution of disease. Patients can be treated on ambulatory basis with low cost and low absorbed dose.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 8:182513 : Efficacy of 30 mCi I-131 in remnant thyroid ablation for differentiated thyroid carcinoma: A single-institution experience

A Sreekumar ¹, Lekha M Nair ¹, V M Pradeep ¹

Rationale: The optimal dose of radioiodine needed for remnant ablation has been widely studied. However, no consensus has been reached for the same. Most studies have shown successful ablation with doses of 1110–1850 MBq (30–50mCi). Few studies have advocated high doses of 3700–5550 MBq (100–150 mCi) for remnant ablation. Advantages of low-dose radioiodine treatment are convenience of outpatient treatment, reduced whole-body radiation exposure, and low cost. It also delays the waiting period for the treatment. After Atomic Energy Regulatory Board has approved permission for treatment with up to 30 mCi I-131 as outpatient basis, we took up this pilot study. In this retrospective study, we analyzed the efficacy of 30 mCi radioiodine for remnant thyroid ablation in patients with differentiated thyroid cancers treated at our institute.

Objective: To retrospectively analyze the efficacy of 1110 MBq (30 mCi) radioiodine for remnant thyroid ablation in patients with differentiated thyroid cancers.

Materials and Methods: Data of 202 patients with differentiated thyroid cancers who received 30 mCi radioiodine for remnant thyroid ablation after total or near-total thyroidectomy, from 2014 to 2016, were analyzed 6–9 months after ablation. Follow-up whole-body scan to assess ablation success was done 6–9 months after ablative dose. Stimulated thyroglobulin (Tg) values and anti-Tg values were measured before the follow-up scan. Criteria for successful remnant ablation were taken as (1) absence of residual thyroid tissue in thyroid bed and (2) stimulated Tg <2 ng/ml with normal anti-Tg titer.

Results: 65.8% of patients’ attained successful ablation of residual thyroid in postablation follow-up scan. 57.9% of patients attained a stimulated Tg value of <2 ng/ml duringfirst follow-up. 46.3% of patients satisfied both the criteria. Female gender was associated with better successful ablation rate than male gender in univariate analysis (P = 0.0016). Patients with preablation Tg value <4 ng/ml was found to have better successful ablation compared to those with higher Tg value (P = 0.0029). In multivariate analysis, both preablation Tg and gender remained to be statistically significant (P = 0.002 and 0.003, respectively).

Conclusion: Radioiodine treatment with 30 mCi for residual thyroid ablation showed success rates of 46.8% taking both scan and Tg criteria at thefirst posttreatment follow-up.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 9:165050 : Radioiodine therapy in a thyroid cancer patient with chronic renal failure on hemodialysis: Therapeutic challenges and radiation safety issues

Pravind Maletha ¹, Kamaldeep ¹, Gaurav Malhotra ¹, Digish Shah ¹, Rohit Ranade ¹, Sushma Kaisar ¹, ShriramTervankar ¹, Ashok Kriplani ¹, Ramesh Asopa ¹

Rationale: Patients of end-stage renal disease (ESRD) have higher incidence of cancer particularly thyroid cancer. Adjuvant radioiodine therapy in a patient of differentiated thyroid cancer on hemodialysis due to ESRD can be challenging since the major route of elimination of radioactive iodine is urine, and there are no recommendations in the literature on their management. We present a known case of chronic renal failure on regular hemodialysis with associated papillary thyroid cancer and lymph node metastasis who underwent adjuvant radioiodine therapy.

Methodology: A 51-year-old female patient of ESRD on chronic hemodialysis was administered adjuvant radioiodine therapy with 5.587 GBq (151 mCi) 1-day after the dialysis. However, on routine monitoring on the 5^th day, she was found to have radiation burden of 120 uSv/h at 1 m distance, thereby requiring immediate dialysis as a life-saving measure. Hence, she was shifted from isolation ward to artificial kidney unit (AKU) for hemodialysis. Radiation survey was performed inside and outside the ambulance at the time of shifting. Similarly, radiation dose received by the persons accompany the patient and the dialysis staff in AKU were recorded with direct reading dosimeter (DRD). Radiation survey and swipe sampling of the procedure area was also performed.

Key Result: Following dialysis, the dose rate of patient decreased from 125 uSv/h to 45 uSv/h at 1-m distance. Maximum dose received by the radiation workers was 21–24 uSv. Radiation survey after dialysis revealed dose rate corresponding to background levels (88–110 nSv/h). Total cumulative dose was 218 person-uSv with average dose of 43.6 uSv and maximum dose of 76 uSv which was received by patient's caregiver.

Research Highlight: Where necessary patients of ESRD can receive radioiodine followed by hemodialysis as a life-saving measure, even if the radiation burden is not within the permissible limit for discharge, but it cannot be recommended as a routine practice. Dose received by the caregiver, radiation worker, dialysis equipment, and procedure area were more than that expected from a routine therapy of this nature. However, it was well with the permissible limits owing to proper planning and appropriate safety measure. Multidisciplinary approach involving the nuclear medicine physician, radiation safety officer, and nephrologists is the key to achieve desired outcome.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 10:203730 : Assessment of salivary gland function using scintigraphy in patients with Sjögren's syndrome

L Peethamber ¹, Nandini Pandit ¹, H Dhanapathi ¹, P Madhusudhanan ¹

Rationale/Objective: The aim of the study was to assess salivary gland function by scintigraphy in patients with Sjögren's syndrome (SS) and to compare with controls.

Methods: The study included 167 cases and 75 controls (patients referred for thyroid scan without salivary dysfunction) from 2013 to 2017. Participants were assessed for xerostomia by oral-based xerostomia questionnaire (XQ) and underwent salivary gland scintigraphy (SGS). Quantitative parameters such as maximum accumulation at 15^th min (MA%), excretion fraction (EF%), and secretion velocity (SV%) were calculated by region of interest analysis.

Results: The mean age (standard deviation) in cases was 42.34 (11.64) years and was comparable with controls 40.97 (12.79) years. Parotid gland (PG) parameters, EF% and SV%, have shown statistically significant difference between cases and controls (P <0.001; P = 0.001). MA% of PG did not show any statistically significant difference between cases and controls (P = 0.285). Submandibular gland (SG) parameters, EF%, SV%, and MA%, have shown statistical significant difference between cases and controls (P = 0.008; P = 0.012; P = 0.034). In the study, the correlation between the xerostomia score and SGS parameters in cases was neither statistically significant (P > 0.05) nor correlative (r < 0.7).

Conclusion: Quantitative parameters such as EF% and SV% in PG and EF%, SV%, and MA% in SG may be considered sensitive for diagnosing SS. No statistically significant correlation was found between xerostomia score derived from XQ and quantitative parameters in cases. Further studies have to done to validate XQ in patients affected with SS and to correlate with quantitative parameters of SGS.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Cardiology: OP 11:183308: Clinical outcome of patients with previous myocardial infarction and left ventricular dysfunction assessed with myocardial technetium-99m sestamibi single photon emission computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Rohit Kakde ¹, Ameya Puranik ¹, Archi Agrawal ¹, Sneha Shah ¹, Nilendu Purandare ¹, V Rangarajan ¹

Rationale: Myocardial viability was assessed by technetium-99m sestamibi single photon emission computed tomography (99mTc MIBI SPECT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (F18 FDG PET) to evaluate the prognosis and treatment strategy of patients with myocardial infarction (MI) and left ventricular (LV) dysfunction.

Methodology: Fourteen patients with previous MI and LV dysfunction who underwent 99mTc MIBI SPECT and F18 FDG PET/CT were followed for 6 months postintervention. Distributions of the two radiotracers were classified into two patterns: viable and nonviable myocardium. Cardiac death, acute MI, and unstable angina experienced by patients during follow-up were defined as cardiac events.

Key Results: Out of the 14 patients, nine patients had viable and five had nonviable myocardium. Out of the nine viable patients, eight had clinical improvement and one showed no clinical improvement. Out of five nonviable patients, three had no clinical improvement and two showed clinical improvement postintervention. The sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 80%, 75%, 89%, 60%, and 78.5%, respectively.

Conclusion: Assessment of myocardial viability using hybrid 99mTc MIBI and F18 FDG PET/CT can predict clinical outcome and is helpful in decision-making in the treatment strategy of patients with MI and LV dysfunction. However, more number of patient population and clinical data are required to get better results.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 12:150838 : Optimization of reconstruction parameters in ordered subset expectation maximization and comparison with filtered back projection reconstructed images in technetium-99m sestamibi myocardial perfusion single photon emission computed tomography in Indian population

Pankaj Dheer ¹

Aim of the Study: To determine the most appropriate ordered subset expectation maximization (OSEM) parameters for image reconstruction in technetium-99m sestamibi (Tc99m-MIBI) myocardial perfusion single photon emission computed tomography (MPS) in Indian population and comparison with filtered back projection (FBP) reconstructed images.

Materials and Methods: Studies of 45 patients were retrospectively analyzed. One-day stress-rest Tc99m-MIBI MPS images were reconstructed with OSEM using 16 combinations of different iterations and subsets, i.e., 2-2, 2-6, 2-10, 2-16, 4-2, 4-6, 4-10, 4-16, 6-2, 6-6, 6-10, 6-16, 8-2, 8-6, 8-10, and 8-16. Images were reconstructed both with and without postreconstruction Butterworth filter with frequency and order of 0.4 and 10 for stress and 0.52 and 5 for rest images, respectively (total=1440 reconstructed images, 32 combinations per patient). These images were graded by two blinded nuclear medicine physicians and scoring performed on a scale of 1–4 (4=best image quality) to determine the most appropriate OSEM parameters for image reconstruction. Further, the best OSEM images with/without postreconstruction Butterworth filter were compared with the FBP reconstructed image using standard parameters.

Results: The most appropriate input parameters of OSEM for reconstruction of Tc99m-MIBI MPS were found to be four iterations and six subsets with/without postreconstruction Butterworth filter. In addition, the images reconstructed using OSEM with postreconstruction Butterworth filter were better than the images reconstructed using FBP. However, for the images reconstructed using OSEM without postreconstruction Butterworth filter, FBP images were found to be better.

Conclusion: The most appropriate OSEM parameters for image reconstruction in Tc99m-MIBI MPS was four iterations with six subsets with postreconstruction Butterworth filter in our study.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 13:202556: Preoperative evaluation of myocardial perfusion and ventricular function in chronic liver disease patients being planned for liver transplantation: A tertiary care center experience

Yeseshvi Kilambi ¹, Madhusudhanan Ponnusamy ¹

Objectives: To assess of left ventricular (LV) myocardial perfusion and function abnormalities in patients with chronic liver disease (CLD) who are being planned to undergo liver transplantation.

Methods: Images of CLD patients who underwent technetium-99m sestamibi (Tc-99m MIBI) stress myocardial perfusion scan as part of preoperative evaluation during the period December 2016 to September 2017 were evaluated. The study was done on one-day stress-rest protocol or as a stress-only scan. The scans were interpreted by the nuclear medicine physicians who had access to the clinical history of the candidates, risk factors, scan images, and its semi-quantitative results (i.e., quantitative perfusion single photon emission computed tomography/computed tomography (SPECT/CT) and quantitative gated SPECT/CT). Visual interpretation of myocardial perfusion imaging (MPI) studies (normal or abnormal with the coronary artery territory involved), LV ejection fraction, and regional wall motion abnormality data were collected and analyzed.

Results: Total number of patients was 23 and all were male (median age 45, interquartile range of 42–52). Three of the patients had pre-existing ECG abnormalities and one had global LV hypokinesia on echocardiography during preoperative workup and the rest had normal electrocardiographic and echocardiographic findings. Sixteen underwent stress-only protocol (treadmill – 10, adenosine – 6). Three patients (12.5%) had perfusion defect (2 had mild degree ischemia and 1 had scar). Territory-wise distribution was left anterior descending (LAD) - 3, left circumflex - 1, and right coronary artery territories - 1. Dilated LV cavity was found in nine patients (39%), and one of them had LAD territory scar. The same patient showed global LV hypokinesia with an ejection fraction of 25%.

Conclusion: Three out of 23 patients had evidence of ischemic heart disease. Stress MPI is useful in assessing risk of coronary events in patients who are scheduled to undergo liver transplantation.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 14:160229: Comparison of left ventricular phase parameters analysis between different software programs in patients with normal-gated single photon emission computed tomography-myocardial perfusion imaging

Dharmender Malik ¹, Ashwani Sood ¹, Madan Parmar ¹, Bhagwant Rai Mittal ¹

Rationale: Phase analysis can be easily performed by different software to assess the left ventricular dyssynchrony from gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with high precision. However, the normal values of histogram bandwidth (HBW) and phase standard deviation (PSD) and their comparison using different programs has not been fully elucidated and actively being evaluated at present. The aim of this study was to determine the phase analysis parameters values and to compare the phase indices of two commonly used programs in a group of patients with normal-gated SPECT-MPI.

Methodology: Phase parameters were retrospectively evaluated in 138 consecutive nondiabetic patients having normal-gated SPECT-MPI using the Quantitative-Gated SPECT (QGS) and Emory Cardiac Toolbox (ECTb) software. HBW, PSD, and phase entropy were calculated separately using both programs by two experienced nuclear medicine physicians who were blinded to the study.

Key Results: The fair correlation between software programs was observed. HBW and PSD in QGS and ECTb were 26.20 ± 9.7 and 25.46 ± 8.0 (r = 0.56, SEE 6.65) and 6.64 ± 2.5 and 7.65 ± 2.5 (r = 0.54, SEE 2.14), respectively. The value of phase entropy in QGS program was 45.08 ± 6.3. A fair correlation between phase entropy and PSD in QGS was observed (r = 0.44, 95% confidence interval 0.29–0.56).

Research highlights: Phase analysis parameters derived from gated SPECT-MPI in patients with normal myocardial perfusion are program dependent and may differ. The results cannot be interchangeably used in the same patients.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

PET-MR/PET-CT/SPECT: OP 15:142857: Role of prostate-specific membrane antigen positron emission tomography/computed tomography in initial staging of prostate cancer patients with low serum prostate-specific antigen

Aravintho Natarajan ¹, Nihit Mhatre ¹, Archi Agrawal ¹, N C Purandare ¹, Sneha Shah ¹, Ameya Puranik ¹, Ganesh Bakshi ¹, Gagan Prakash ¹, Vedang Murthy ², Santosh Menon ³, Amit Joshi ³, Rahul Krishnatry ², Mahendra Pal ¹, V Rangarajan ¹

Rationale: 68Ga-prostate-specific membrane antigen (PSMA) (N, N′-bis- [2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N, N′-diacetic acid) is a novel PSMA-ligand used for prostate cancer imaging. The aim of this retrospective study was to investigate role of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in staging of newly diagnosed prostate cancer patients with low serum prostate-specific antigen (PSA) (<20 ng/ml).

Methodology: Data and images of all consecutive newly diagnosed prostate cancer patients with serum PSA less than 20 ng/ml at the time of scan were retrospectively analyzed. Patients who received hormonal treatment before the scan were excluded. All patients underwent contrast-enhanced PET/CT after injecting 1.7–2.5 mCi 68Ga-PSMA-ligand. Detection rate for regional and distant metastases was calculated and correlated with PSA level and Gleason's score. Detection rate of PSMA PET/CT for nodal metastases was compared with CT.

Key Results: A total of 144 patients were eligible for analysis. The mean PSA level of the population was 9 (range: 0.2–19.9) and median Gleason score was 8. Metastases were detected in 58 (40.2%) patients. Regional node metastases (N1), nonregional node metastases (M1a), bone metastases (M1b), and other distant metastases (M1c) were detected in 48 (33.3%), 17 (11.8%), 32 (22.2%), and 7 (4.9%), respectively. PSMA PET/CT had incremental value over CT scan in 25 (52%) and 5 (29.4%) patients with regional and nonregional node metastases, respectively. No significant association between PSA level and metastases was found (P = 0.7 by Spearman rank correlation), but Gleason's score had strong correlation with metastatic finding in scan (P< 0.05). Detection rate for metastases at various Gleason's score were 5% for Gleason's score of 6, 19.6% for score 7, and 64.3% for score ≥ 8.

Research Highlights: PSMA PET/CT can detect regional and distant metastases in treatment naïve prostate cancer patients with low serum PSA and is superior to CT scan in detection of nodal disease. The detection rate has strong positive correlation with Gleason's score.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 16:130124 : Positron emission tomography-computed tomography imaging of chloromas in acute myeloid leukemia: A prospective study

Nalli Harish ¹, Sameer Bakhshi ¹, Chetan Patel ¹, Anshul Sharma ¹, Ravikant Gupta ¹, Akshima Sharma ¹, Chandra Shekar Bal ¹, Rakesh Kumar ¹

Rationale: Myeloid sarcoma or chloroma is an extramedullary involvement seen in 3%–5% of acute myeloid leukemia (AML) cases. It can both predate the AML by months or can be an initial manifestation of a relapse. Bone marrow biopsy (BMB) is typically used for diagnosis as well as assessment of treatment response. However, BMB cannot identify all medullary involvement as well as extramedullary involvement. The enhancement pattern on computed tomography (CT) and magnetic resonance imaging is quite variable.

Objectives: The present study was aimed to evaluate the role of hybrid imaging with positron emission tomography/CT (PET) to identify the sites of extramedullary involvement while simultaneously evaluating the intramedullary disease in patients of AML.

Materials and Methods: A total of six AML patients with biopsy-proven chloromas were prospectively evaluated using 18F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT for extramedullary and intramedullary disease involvement. PET/CT images were evaluated by two nuclear medicine physicians. Maximum standardized uptake values (SUVmax) of all the identified lesions were measured.

Results: A total of six patients (4 males, 2 females), with a mean age 11.3 years (6–19 years) were enrolled till date for this prospective study. On FDG PET/CT, a total of 31 lesions were identified and divided into three groups as masses (n = 15), lymph nodes (n = 6), and soft tissue deposits (n = 10). Five patients presented with masses in head and neck region; one presented with a breast nodule and another with an intramedullary lesion. The mean of SUVmax of mass lesions was 5.22 ± 1.96. Five patients had soft tissue deposits which included pleura, spleen, prevertebral and intra-spinal deposits, and mean SUVmax 2.99 ± 0.95.

Conclusion: ¹⁸F-FDG PET/CT plays an important role in detecting medullary as well as extramedullary lesions in the patients with AML. Therefore, PET/CT can be used for evaluation of the extent, treatment response, and recurrent disease in these patients.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 17:141342 : Correlation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and single photon emission computed tomography/computed tomography in the detection of regional lymph node metastases in early-stage oral cancer

Meetashree Nayak ¹, M Indirani ¹, S Shelley ¹

Background: Prevalence of oral cancer is 45% in India. Patients with N0 neck have 30% occult metastases, but all patients undergo neck node dissection, so 70% of them are over-treated and subjected to the surgical morbidity. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and single photon emission computed tomography (SPECT)-CT are two diagnostic modalities for detection of regional lymph nodes (LNs).

Aim: To correlate 18 F-FDG PET/CT and SPECT/CT in the detection of regional LN metastases by comparing with the gold standard (biopsy).

Methodology: Thirty patients with histologically confirmed oral squamous cell carcinoma with clinically N0 neck were included. FDG PET-CT 1 day before and SPECT/CT 2 h before the surgery was performed. Besides the LN positive either in FDG PET/CT or SPECT/CT, LN showing higher count in gamma neoprobe was also removed and sent for biopsy.

Results: Out of 30 patients, nine were positive in FDG PET/CT (8 were true positive [TP] and one was false positive [FP]), 21 found to be negative (19 were TP and 2 were false negative [FN]). In SPECT/CT, out of 26 cases (sentinel LN seen), 22 are TP and four are FP for metastases. Out of 4 negative cases, one is TN and three are FN. Hence, sensitivity and specificity of FDG PET/CT are 80% and 95% and of SPECT/CT are 88% and 20%, respectively.

Conclusion: SPECT-CT is sensitive in detection and anatomical localization of sentinel LN, but FDG PET/CT can distinguish malignant LN from benign. Hence, preoperative combined use of FDG/PET and SPECT/CT can increase the accuracy in the detection of regional LN metastases.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 18:171302 : Impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on nodal volumes during radiotherapy planning in recently diagnosed cases of locally advanced carcinoma breast

S Muneendra Kumar ¹, Ranadheer Mantri ¹, Swapna Jilla ¹, H Narendra ², A Y Lakshmi ³, Tekchand Kalawat ¹

Rationale: (1) To evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG PET/CT) in eliciting gross nodal volume during radiotherapy planning in recently diagnosed cases of locally advanced carcinoma breast. (2) To evaluate the role of 18F FDG PET/CT in accurate nodal staging in recently diagnosed cases of carcinoma breast.

Methodology: We retrospectively evaluated 94 treatment naive cases of carcinoma breast, who were referred for initial staging purpose from January 2013 to August 2017. All the patients underwent 18F FDG PET/CT scan by following the standard procedure guidelines. CT and fused PET/CT images were opened and analyzed simultaneously. Images were analyzed and interpreted by visual observation (qualitatively) and using semi-quantitative analysis of FDG uptake.

Key Results: A total of 94 patients with recently diagnosed Locally advanced carcinoma breast were evaluated with 18F FDG PET/CT. Internal mammary lymph nodes were detected in 23/94 patients (24.4%), supraclavicular lymph nodes were detected in 12/94 patients (12.7%) and infraclavicular lymph nodes were detected in 11/94 patients (11.7%), all the three nodal stations were involved in 2/94 patients (2.1%), internal mammary and supraclavicular nodes were involved in 3/94 patients (3.1%), internal mammary and infraclavicular in 2/94 patients (2.1%), and supraclavicular and infraclavicular lymph nodes were involved in 2/94 patients (2.1%). In 39/94 (41.4%) patients, there is change in management of patients with 18F FDG PET/CT.

Research Highlights: 18F FDG PET/CT helps in accurate nodal staging. Thus, it has a significant role in eliciting nodal volumes in radiotherapy planning in locally advanced breast carcinoma patients.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 19: 154326 : Sequential imaging with parathyroid scintigraphy/single photon emission computed tomography-computed tomography and ultrasonography in cases of hyperparathyroidism for parathyroid adenoma localization

S D Abdul Rahim ¹, S Shelley ¹, M Indirani ¹

Background: Parathyroid scintigraphy/single photon emission computed tomography (SPECT)-CT and ultrasonography are the primary imaging modalities used for the demonstration of diseased parathyroid glands. Parathyroid scintigraphy/SPECT-CT is approximately 90% sensitive for parathyroid adenoma localization and can easily visualize parathyroid glands greater than 500 mg. Ultrasonography is 60%–80% sensitive for adenoma localization and can localize lesions above 1 cm.

Aim: To evaluate the role of sequential imaging with parathyroid scintigraphy/SPECT-CT and ultrasonography in cases of hyperparathyroidism for parathyroid adenoma localization.

Materials and Methods: The study consisted of 16 patients of hyperparathyroidism of which 7 were males and 9 were females. Sequential imaging was done with parathyroid scintigraphy/SPECT-CT and ultrasonography to localize the lesion, these were followed till surgery, and histopathology positive cases for parathyroid adenoma were taken.

Results: Out of 16 patients who were histopathology positive for parathyroid adenoma, 15 were detected to be positive for parathyroid lesions with parathyroid scintigraphy/SPECT-CT and 11 were positive for parathyroid lesions with ultrasonography. Ten cases were positive for both. One (6%) patient who was positive for parathyroid lesion on ultrasonography was negative with parathyroid scintigraphy/SPECT-CT; 5 (31.2%) patients who were positive for parathyroid lesion with parathyroid scintigraphy/SPECT-CT were negative with ultrasonography.

Research Highlights: Sequential imaging with both parathyroid scintigraphy/SPECT-CT and ultrasonography may improve sensitivity to localize parathyroid adenoma before surgery.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 20:174632 : In silico, synthesis, and preliminary evaluation of benzothiazolone-diethylene-triamine-pentaacetate acid-conjugates: ^99mTc-DTPA-(BTZ)₂ and ^99mTc-DTPA-(Ac-BTZ)₂ as single photon emission computed tomography neuroimaging agents

Preeti Jha ^1,², Shubhra Chaturvedi ¹, Ankur Kaul ¹, Sunil Pal ¹, Nidhi Jain ², Anil K Mishra ¹

Rationale: The affinity of a radiotracer can be fine-tuned by increasing the number of biomarkers attached to a chelator. Herein, we report the synthesis and preclinical evaluations of bifunctional chelating agents: ^99mTc-DTPA-(BTZ)₂ and ^99mTc-DTPA-(Ac-BTZ)₂ as single photon emission computed tomography (SPECT) imaging agents for 5-HT_1A and 5-HT₇ neuro-receptors. These neuro-receptors are majorly expressed in the hippocampus of the brain and represent an important target for the treatment of depression, anxiety, and mood regulation. Imaging of 5-HT_1A/5-HT₇ receptors can thus be utilized to assess the quantitative and functional aspect of neurological disorders.

Methodology: The benzothiazolone (BTZ) based BTZ-diethylene-triamine-pentaacetate acid (DTPA)-conjugates were designed on the basis of physicochemical parameters and the K_i values reported for the similar kind of structures. 3D-structures of 5HT_1A and 5-HT₇ receptors were generated using homology modeling. The synthesized compounds were characterized using ultraviolet–visible, nuclear magnetic resonance, and mass spectrometry. Hemolysis and cytotoxicity studies were performed on human blood and HEK-293 cell line. Radiolabeling was achieved with 98% labeling efficiency. The in vitro receptor binding affinity and bio-distribution studies ensures the affinity and selectivity. The specificity for brain imaging was analyzed via in vivo SPECT imaging.

Research Highlights: Receptor-ligand interactions revealed the presence of conserved residues in active binding pockets of 5-HT_1A and 5-HT₇ receptors. No significant cytotoxicity was observed at concentration range of 1 nM–1 mM. Less than 5% toxicity in hemolysis showed intravenous injection feasibility. The in vivo bio-distribution studies showed maximum uptake in brain corresponding to 2.1% ID/g for HB-DT. The bio-distribution studies of AHB-DT are underway. Significant uptake in receptor-rich regions of the brain indicates affinity and specificity for the 5-HT_1A/5-HT₇ receptors. The uptake in kidney indicated renal route of excretion. More than 95% ^99mTc-binding were observed in cysteine challenge study.

Conclusion: Novel neuroimaging agents ^99mTc-DTPA-(BTZ)₂ and ^99mTc-DTPA-(Ac-BTZ)₂) to target 5-HT_1A/5-HT₇ receptors were theoretically evaluated, synthesized, and evaluated preclinically.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 21:152259 : Semi-quantitative striatal-to-occipital ratios on L-3,4-dihydroxy-6-F-18 fluorophenylalanine brain positron emission tomography in idiopathic Parkinson's disease

Harish Goyal ¹, Madhavi Tripathi ¹, Vinay Goyal ¹, Anshul Sharma ¹, Chetan D Patel ¹, Chandrasekhar Bal ¹

Objective: To evaluate striatal-to-occipital ratios (SOR) on L-3,4-dihydroxy-6-F-18 fluorophenylalanine (FDOPA) positron emission tomography (PET) in early and advanced idiopathic Parkinson's disease (IPD) based on clinical rating scales – unified Parkinson disease rating scale (UPDRS) and Hoehn and Yahr (H&Y) scale. Since an underlying serotonergic deficit is the pathophysiology in tremor predominant IPD, we derived midbrain-to-occipital ratio (MOR) on FDOPA PET in this subgroup.

Materials and Methods: We evaluated a total of 20 IPD patients with FDOPA PET brain. Each patient underwent dopaminergic imaging after undergoing a detailed clinical examination at the movement disorder clinic of our institute. This included nine early IPD (UPDRS = 30.3 ± 5.6; range 19–36, H&Y < 2.0 and disease duration = 3.4 ± 0.9; range 2–5 years) and 11 advanced IPD (UPDRS = 54.3 ± 7.2; range 44–66 and H&Y = 2.0–4.0, disease duration = 6.6 ± 3.2; range 4–14 years). Twelve patients who had undergone FDOPA PET for reason other than Parkinsonism were included as control. Regions of interest were generated for the caudate, putamen, occipital regions, and midbrain on fused PET images for structural correlation. SORs were generated for caudate and putamen and MOR for midbrain. Statistical analysis using Mann–Whitney U-test was performed between controls to early and advanced IPD separately. MOR was compared between non-tremor dominant and tremor predominant IPD (assessed by UPDRS tremor score).

Results: SOR clearly differentiated between controls and early as well as advanced IPD (P = 0.006 and 0.003, respectively). SOR between early and advanced IPD patients was also significantly different (P = 0.018). Comparison between contralateral SOR (to predominant symptom sidedness) to ipsilateral SOR was significantly different in early IPD (P = 0.032) while no significant difference was noted for advanced IPD (P = 0.507). MOR in tremor predominant subgroup showed significant difference from nontremor dominant subgroup group (P = 0.002).

Conclusion: SOR is a good diagnostic tool for IPD patients and can differentiate between early and advanced IPD. SOR correlates well with clinical sidedness in early IPD but not in advanced IPD. MOR can be used in the tremor predominant patient subgroup when SORs may not be useful.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 22:213025 : Semi-quantitative analysis of technetium-99m-methionine brain single photon emission computed tomography in differentiation of brain tumor recurrence from radiation necrosis: A comparison with perfusion MRI

N Rani ¹, B Singh ¹, N Kumar ¹, P Singh ¹, P Hazari Puja ¹, A Jaswal ¹, M Kumar A K Mishra ¹, A Bhattacharya ¹, A Kohli ¹, S Gupta ¹

Rationale: We used an amino acid-based homodimeric methionine derivative-labeled with technetium-99m (^99mTc) for the detection and differentiation of recurrent/residual glioma from radiation necrosis. The results of bis-methionine-diethylene-triamine-pentaacetate acid single photon emission computed tomography (MDM-SPECT)/CT were compared with DSCE-MRI. Proposed comparative diagnostic accuracy of ^99mTc MDM-SPECT/CT to dynamic susceptibility contrast-enhanced-magnetic resonance imaging (DSCE-MRI) would be a cost-effective method in the management of glioma.

Methodology: Twenty-eight (18M:10F; mean age= 41.4 ± 15.03 years) patients with histological-proven glioma (14-G-IV; 07-G-III; 07-G-II) who were planned for postsurgical standard radio/chemo-therapy were recruited prospectively. All the patients underwent both imaging at 6 months postsurgery/radio/chemo-therapy. Nine patients also underwent SPECT imaging at 1–2 weeks postsurgery.

Key Results: SPECT and DSCE-MRI data analysis (39 scans each) demonstrated significantly higher (3.59 ± 1.70) target to nontarget ratio of the radiotracer in tumor recurrence then (1.16 ± 0.42) in radiation necrosis. Likewise, the normalized mean relative cerebral blood volume (rCBV) values in patients with tumor recurrence were higher 5.16 ± 2.30 versus 1.63 ± 0.94. A positive correlation (rho = 0.823, P < 0.0001) between lesion to background ratio (LBR) and nCBV - normalized cerebral blood volume was observed. Receiver characteristic curve analyses evaluated cutoff values as an evidence of tumor recurrence and were >1.50 (area under the curve 0.944 ± 0.34) and >2 (AUC 0.931 ± 0.39) for LBR and normalized cerebral blood volume, respectively. Combining the results of ^99mTc-methionine SPECT, DSCE-MRI, and clinical findings, a final diagnosis of recurrent/residual glioma and radiation necrosis was made in 18 and 10 patients, respectively. Sensitivity and specificity for these two techniques were comparable (92%:78.6% - SPECT; 92%:71.4% - DSCE-MRI).

Research Highlights: Therefore, 99mTc-methionine SPECT as a cost-effective substitute to expensive positron emission tomography imaging has comparable diagnostic utility with DSCE-MRI and thus may have a complementary role in the diagnostic workup of glioma patients.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 23: 162419 : Theranostic potential of nucleo lipidic liposomal assemblage for drug delivery in brain

Swastika Mishra ¹, Shubhra Chaturvedi ¹, Ankur Kaul ¹, Puja Panwar Hazari ¹, Preeti Jha ¹, Sunil Pal ¹, Philippe Barthélémy ¹, B Singh ², A K Mishra ¹

Rationale: Limited drug availability in the brain due to the blood–brain barrier (BBB) necessitates the need for an efficient drug delivery system (DDS). Nucleolipids (nucleoside + lipids, NL) based DDS offer enhanced permeation through the biological membranes. In addition, NL-liposomal assemblage can be loaded with drugs and modified for targeted delivery. The targeted delivery is based on the enhanced uptake of nucleosides at the diseased site. Single photon emission computed tomography (SPECT) imaging of radiolabeled NL-liposome can also assist in tracking. In this work, uridine-NL liposome for the delivery of antitumor and antibiotics in the brain has been formulated and studied. To ascertain the targeting of the liposomes, the liposomes have been modified as a SPECT tracer.

Methodology: Uridine was chemically modified and appended with lipidic chain at 2’-3’ and diethylenetriaminepentaacetic acid (DTPA) at 5’. Liposomes were formulated through nano-precipitation. Thorough chemical, physical, biological, and pharmacological characterization was carried.

Key Results: After nuclear magnetic resonance, mass spectrometry, and analytical characterization of the intermediates and NL conjugate (NL-DTPA), liposomes of size 100–150 nm with good zeta potential of −14 mV were obtained. Transmission electron microscopy ascertained the spherical morphology. Stable, non-toxic preparation with high technetium-99m radiolabeling efficiency >98% was obtained which showed considerable brain uptake (≈0.84% I.D/gm) in mice. Experiments with encapsulated drugs indicate diffusion-controlled release. Fluorescence imaging with encapsulated rhodamine-drug conjugate is underway.

Research Highlights: NL-based drug delivery system capable of targeting BBB-uncompromised brain has been studied for physicochemical, pharmacological, and drug delivery parameters.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 24:235057 : [¹⁸F]-fluoro-ethyl-L-tyrosine positron emission tomography-computed tomography: A valuable diagnostic tool in brain tumors

Hitesh Aggarwal ¹, Maria D’souza ¹, Puja Panwar ¹, Sanjiv Saw ¹, Santosh Pandey ¹, Yachna Solanki ¹, Shalu Meena ¹, Harish Rawat ¹, Nitin Kumar ¹, Rajnish Sharma ¹, Anil K Mishra ¹

Rationale: 18-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neuro-oncology. FET reflects amino acid transfer and has been shown to be more sensitive than MRI in stereotactic biopsy planning. This study compared FET PET-CT and fluorodeoxyglucose (FDG) PET-CT in detection of various brain tumors and brain metastasis.

Methodology: Twenty-one subjects of brain tumor treated by surgery, chemotherapy, and radiotherapy were subjected to FDG and FET scan. The lesions were analyzed semi-quantitatively using tumor to normal contra-lateral uptake ratio. Dynamic scan was taken for FET PET-CT and an uptake time graph was plotted for the lesions reported as positive on the scan. Diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, magnetic resonance imaging (MRI), or CT scan.

Key Results: Tumor recurrence was found in only four out of 21 patients on FDG scan while FET PET was able to detect recurrence in 16 out of 21 patients. Four patients in which FDG scan was positive were found to have peak tumor uptake at 15 min in FET scan and were found to be high-grade gliomas in postoperative biopsy. The other 12 FET-positive cases showed peak tracer uptake at 30–40 min and were found to be low-grade gliomas. No false positive cases were reported in the study; however, one patient who was FET as well as FDG negative was found to have low-grade glioma which was also appreciated in CT and MRI images. On semi-quantitative analysis, mean target/nontarget (T/NT) ratio was found to be 3.5 ± 0.94 in lesions positive for tumor recurrence in FET scan, while in FDG scan, T/NT ratio was found to be 2.05 ± 1.04 in lesions positive for tumor recurrence.

Research Highlights: The study highlights that FET PET-CT is superior to FDG PET-CT in detecting recurrent brain tumors. Time of peak uptake value is also an important parameter in determining grade of gliomas noninvasively. Therefore, amino acids such as (18)F-FET are the preferred PET tracers for the clinical management of brain tumors.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 25:155321 : Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in evaluation of immunoglobulin G4-related disease

Ashwin Singh Parihar ¹, Rajender Kumar ¹, Harmandeep Singh ¹, Apurva Sood ¹, Tinu Lukose ¹, Shelvin Kumar Vadi ¹, Anish Bhattacharya ¹, Bhagwant Rai Mittal ¹

Rationale: Immunoglobulin G4-related disease (IgG4RD) is a multi-system disease complex with no specific etiology. The disease process is known to involve the exocrine glands, kidneys, lungs, lymph nodes, etc. Currently, role of conventional modalities in assessment of disease diagnosis, extent and severity is limited. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) being a molecular/functional imaging technique has the potential to provide valuable information in this aspect.

Methodology: We retrospectively analyzed 10 previously untreated patients with clinical and biochemical suspicion of IgG4RD, who had undergone ¹⁸F-FDG PET/CT from November 1, 2016, to August 31, 2017. Analysis was done on the basis of qualitative and semi-quantitative parameters (maximum standardized uptake value [SUV_max]).

Key Results: Mean age of the 10 patients (M:F=1:1) was 37.1 ± 24.1 years. The most common presenting complaint was abdominal pain (5/10). Disease involvement of two or more sites was noted on ¹⁸F-FDG PET/CT in all the patients. The disease spectrum on ¹⁸F-FDG PET/CT included palatine tonsils (6/10, mean SUV_max6.7), lymph nodes (5/10, SUV_max7.1), salivary and lacrimal glands, lungs, bile ducts, kidneys, esophagus, pancreas, spleen, and retroperitoneum, in the decreasing order of frequency, which was consistent with the pattern, in literature. The maximum ¹⁸F-FDG uptake was noted in the axillary lymph nodes (SUV_max11.9) and minimum in bile ducts (SUV_max1.2).

Research Highlights: ¹⁸F-FDG PET/CT proved beneficial in the overall assessment of disease extent and severity in these patients and in providing a holistic picture which is not possible with the conventional diagnostic modalities. Thus, ¹⁸F-FDG PET/CT is a useful modality in the primary evaluation of patients with IgG4RD.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 26:181316: Comparative quantitative analysis of fluoro-2-deoxyglucose positron emission tomography hypometabolism in identification of seizure foci by available molecular image processing software

Chandana Nagaraj ¹, Dinesh Kumar ¹, M Sandhya ¹, A K Gupta ¹

Rationale: This was a comparative quantitative analysis of fluoro-2-deoxyglucose positron emission tomography (FDG PET) hypometabolism in identification of seizure foci by available molecular image processing software.

Methodology: The role of 18F FDG PET is a well-established imaging modality in seizure focus localization. 18F FDG PET is widely used and available technique presently. Literature review clearly demonstrates that the sensitivity of interictal 18F FDG PET is similar to ictal single photon emission computerized tomography (SPECT) but definitely higher the interictal SPECT. Lateralization or localization of epileptogenic foci is essential for presurgical evaluation of patients with refractory seizures. The main aim of this study is to correlate the visually seen qualitative most hypometabolic regions of the interictal brain 18F FDG PET with the available quantitative analysis molecular image processing software. This is likely to highlight the different ways of image interpretation and the benefits of quantification, especially the pitfalls of available molecular image processing software.

Key Results: The F18 FDG images of 30 patients referred as a part of presurgical evaluation were processed using commercially available image processing software SCENIUM and MIM neuro. The visually seen areas of hypometabolic areas were quantified using these soft wares. The results of the visual assessment, SCENIUM, and MIM were compared totally blind to clinical details and other investigations.

Research Highlights: The quantitative analysis adds on to the visual assessment thus confirming the findings seen visually. Quantification per se is very important for assessment of any disease. Uniformly one standard method can be adopted for the benefit of the referring physicians.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Radiopharmacy: OP 27:084636: Comparison of ¹⁷⁷Lu-EDTMP, ¹⁷⁷Lu-DOTMP, and ¹⁸⁸Re-HEDP: A preclinical view of therapeutic efficacy

Chandan Kumar ¹, Rohit Sharma ¹, Madhav B Mallia ¹, Tapas Das ¹, Mythilli Kameswaran ¹, Aruna Korde ¹, Ashutosh Dash ¹

Rationale: Bone-seeking radiopharmaceuticals, which selectively deliver ablative radiation dose to the metastatic lesions of bone, are preferred for effective bone pain palliation. There are several bone-seeking radiopharmaceuticals such as ¹⁷⁷Lu-EDTMP, ¹⁷⁷Lu-DOTMP, and ¹⁸⁸Re-HEDP currently being used in the clinics. To identify more appropriate agents, the present in vitro study compares the relative effectiveness of these radiopharmaceuticals in terms of induction of cell death and related phenomena in MG63 osteosarcoma cell line.

Methodology: In-vitro evaluation of ¹⁷⁷Lu-EDTMP, ¹⁷⁷Lu-DOTMP, and ¹⁸⁸Re-HEDP were carried out in MG63 osteosarcoma cell line. Cells were incubated separately with 3.7 MBq of each of these radiopharmaceuticals for 48 h. To investigate the therapeutic efficacy, cellular toxicity and apoptosis were quantified and cell cycle phases were analyzed.

Key Results: All three bone-seeking radiopharmaceuticals exhibited binding to the mineralized bone and induced cell death in MG63 osteosarcoma cells. Effects of all three radiopharmaceuticals were investigated and found that there is no significant difference between ¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-DOTMP in terms of cell toxicity and apoptosis. However, ¹⁸⁸Re-HEDP induced more toxicity and apoptosis compared to both ¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-DOTMP. The cell cycle arrest at G2/M phase was also more pronounced in the ¹⁸⁸Re-HEDP-treated cells.

Research Highlights: ¹⁸⁸Re-HEDP was found to be the most effective among all three radiopharmaceuticals in induction of cell death and cell cycle arrest at G2/M phase in MG63 osteosarcoma cells.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 28:230337 : 131-Iodine-labeled lipiodol: Fully automated synthesis and quality control

Manish Dixit ¹, Nilesh Shankar ¹, Sandeep Singh ¹, Sanjay Gambhir ¹

Rationale: Primary hepatocellular carcinoma is the most common form of primary hepatic carcinoma, particularly in Asia and Sub-Saharan Africa. The therapeutic modalities such as chemotherapy, radiotherapy, and trans-hepatic arterial embolization gave unsatisfactory results. Alternative methods of therapy using lipiodol as a carrier for chemotherapeutic agents or radioisotopes are under investigation. Synthesis of 131-I-labeled lipiodol under strict recommendation of regulatory authority along with worker radiation safety is challenging task.

Methodology: In this study, we describe the fully automated labeling of¹³¹ I with lipiodol, using Sumitomo's CFN MPS-100 automated synthesis module with minor modification in software and module intake of reagents. Synthesis was performed at around 100^o C having mixture of iodized lipiodol (LIPIDOL Ultra Fluid supplied by Guerbet, France) and carrier-free 131-I. The reaction was catalyst by phase transfer catalyst. After 30 min of incubation, the mixer was transfer to product vial by passing through 0.22 μm sterile filter. All quality control tests were performed for being used as clinical product.

Key Results: The overall radiochemical yield was 90% with the labeling purity is more than 98%. The reproducibility of this automated synthesis module is very high.

Research Highlights: Here, we have developed a fully automated synthesizing module such that there is high yield and radiochemical purity and minimal radiation exposure to a radiochemist as per the ALARA.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 29:201944 : Significance of trial labeling before patient dose preparation of ¹⁷⁷Lu-DOTA-TATE

E R Radhakrishnan ¹, S Arun Pandiyan ¹, Indira V Upadhya ¹, Ajit S Shinto ¹, K K Kamaleshwaran ¹

Aim: To ensure sufficiency of DOTA-TATE ligand for patient dose preparation of ¹⁷⁷Lu-DOTA-TATE through trial labeling.

Introduction: ¹⁷⁷Lu has been a potential therapeutic radionuclide for the treatment of inoperable neuroendocrine tumors (NETs) using ¹⁷⁷Lu-DOTA-TATE. This indigenously available radionuclide allows cost-effective preparation of ¹⁷⁷Lu-DOTA-TATE. However, radiolabeling as per the standard calculation based on the quoted specific activity of ¹⁷⁷Lu (molar ration of [DOTA-TATE]:[Lu] =3:1) often results ¹⁷⁷Lu-DOTA-TATE with low radiochemical purity (RCP) which was not acceptable for patient administration. To overcome this undesirable loss of the precious radioactivity, DOTA-TATE and inconvenience caused to the patient, a trial labeling of DOTA-TATE with a smaller amount of ¹⁷⁷Lu-activity (50 mCi) as per standard calculation was carried out. If RCP of the preparation was acceptable, the same protocol was used to prepare patient dose.

Materials and Methods: Indigenously available ¹⁷⁷LuCl₃, DOTA-TATE from ABX, ammonium acetate, gentisic acid, and high-pressure liquid chromatography water.

Methods: To carry out trial labeling, the required amount of DOTA-TATE for ~50 mCi of ¹⁷⁷LuCl₃ was calculated as per the specific activity of ¹⁷⁷Lu. ¹⁷⁷Lu-DOTA-TATE was prepared following the reported protocol. RCP of the preparation was determined following reported QC procedures. If RCP of the preparation was not acceptable, excess amount of DOTA-TATE ligand was used during patient dose preparation to improve the RCP.

Result: Following trial labeling protocol, possible failures in patient dose preparation and associated difficulties were avoided in many occasions.

Conclusion: A trial preparation can be very informative in optimizing the required amount of DOTA-TATE before the final preparation using higher amount of ¹⁷⁷LuCl₃.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 30:111227 : Radiosensitization-mediated efficient delivery of RGD-conjugated doxorubicin in nonsmall cell lung cancer xenografts

Pallavi Sethi ¹, Ambika Parmar Jaswal ¹, Puja Panwar Hazari ¹, Anil K Mishra ¹

Lung cancer is one of the leading causes of death. Combinatorial radiation and chemotherapy are routinely used for treatment of patients with lung cancer. Magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) scan are used in diagnostics of tumor growing or metastasizing within lung tissue. Nodules growing within lung are often diffuse, so surgical resection of all these nodules is not possible. Clinicians often rely on combinatorial therapy to suppress the growth of tumors. Doxil is an FDA-approved drug, currently being used for the treatment of various cancers; however, its use is very limited in nonsmall cell lung cancer (NSCLC). Utilizing in-vitro experiments, we have observed that radiosensitization upregulates the level of integrins on cells of tumor microenvironment. The rationale behind this study is to investigate whether RGD conjugation would facilitate doxorubicin bioavailability in irradiated NSCLC xenograft originated after implanting 3D-tumor tissue analogs. In this study, technetium-99m (^99mTc) radiolabeling with cyclic RGD-doxorubicin conjugate was optimized and evaluated for its accumulation at the tumor site compared to free doxorubicin. The radiolabeled preparation of [^99mTc]-cyclic RGD–doxorubicin and [^99mTc]-doxorubicin remained stable (radiolabeling efficiency approximately 97%–98%) at room temperature for up to 12 h. In-vitro cytotoxicity testing was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on NSCLC tissue analogs. Cellular uptake studies and animal biodistribution studies have been performed using [^99mTc]-cyclic RGD–doxorubicin and [^99mTc]-doxorubicin. Tumor imaging performed in three-dimensional spheroid implanted tumor-bearing nude mice and uptake of the radiotracer was estimated to investigate significance of conjugating RGD peptide. Noninvasive imaging was performed on Trifoil FLEX Triumph 4 (PET/single photon emission computed tomography/CT) System and image reconstruction and analysis was done on AMIRA 4.1.1 software. PET-assisted imaging and biodistribution studies validate that RGD conjugation facilitates accumulation of drugs within tumor site, especially when tumor and its microenvironment are radio-sensitized. In-vivo results confirm the in-vitro finding that radiation can elevate the levels of integrins on tumor site for efficient RGD peptide-based active targeting. In fact, such approach has theranostic value as [99mTc]-cyclic RGD–doxorubicin is being used as a noninvasive radiolabeled imaging agent as well as making the drug available for regressing cells within tumor microenvironment. Labeling drug directly with peptide and imaging agent would be optimal in determining both drug bioavailability and systemic toxicity. By all means, it would be a step toward clinical trials of this formulation considering that all the components are clinically approved.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 31:093227 : Neutral technetium-99m analog of meta-iodobenzylguanidine prepared via technetium-99m(CO)₃ synthon for potential imaging of neuroendocrine tumors

Navin Sakhare ¹, Soumen Das ¹, Anupam Mathur ¹, Madhava B Mallia ¹, Shubhangi Mirapurkar ¹, M Sheela ¹, H D Sarma ², S S Sachdev ¹, A Dash ¹

Introduction: Meta-iodobenzylguanidine (^123/131 I-mIBG) is a clinical agent used for imaging neuroendocrine tumors of neural origin, where the uptake in the tumor is via active transport pathway through norepinephrine transporters (NETs). Our group in the past have evaluated two technetium-99m (^99mTc) analogs based on ^99mTc-4+1 and ^99mTc (CO)₃ designs. The present work attempts to synthesize and evaluate a new neutral derivative based on ^99mTc (CO)₃ approach with an aim to improve uptake and specificity toward NET.

Methods: Precursor 1,3-bis(chloromethyl)benzene was synthetically modified in a five-step procedure to produce benzylguanidine derivative-bearing aminoethylglycine tridentate chelate. This ligand was labeled with ^99mTc via freshly prepared ^99mTc (CO)₃ synthon to yield the desired neutral radioactive complex. The complex was then evaluated in SK-N-SH neuroblastoma cells. Specificity toward NET was ascertained by preincubating the cells with desmethylimipramine, a known blocker for NET. The cell-bound radioactivity was then extracted with 10% (wt/vol) trichloroacetic acid and the activity measured in NaI(Tl) well counter with suitable energy window for ^99mTc (140 Kev ± 10%).

Results: Formation of the synthesized complex was more than 90% as confirmed through high-pressure liquid chromatography. The cell uptake of the radiolabeled complex in SK-N-SH cells was low and specificity too was significantly affected in comparison to standard nca-¹²⁵ I mIBG for different concentrations of the complex studied.

Conclusion: The synthesized complex was designed rationally, but it loses its uptake characteristics via NET and lacked suitability for NET imaging in neuroendocrine tumors.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 32:104319 : Simultaneous synthesis of O-(2’-[¹⁸F] fluoroethyltyrosine and [¹⁸F] fluoromisonidazole using solid phase extraction method

Abhinav Bajpai ¹, N Lakshminarayanan ^1,², Kanchan Khushwaha ^1,², Sharmila Banerjee ^1,²

Rationale: At present scenario, positron emission tomography (PET) radiopharmaceuticals were synthesized with a complete dedicated synthesis for each production starting from cyclotron irradiation till end of synthesis. Simultaneous production of multiple radiopharmaceuticals would of great advantage as a fast and economical process. As an effort to achieve this, O-(2’-[¹⁸F] fluoroethyltyrosine ([¹⁸F]FET) and [¹⁸F] fluoromisonidazole)[¹⁸F] FMISO), chosen based on their polarity difference, were synthesized simultaneously. [¹⁸F]FET is an analog of L-tyrosine, used as brain tumor imaging agent. Fluoromisonidazole ([¹⁸F]FMISO) is a tumor hypoxia imaging agent.

Methodology: Radiolabeling precursors were obtained from ABX, Germany. All other chemicals were purchased locally. ¹⁸F-fluoride production and radiosynthesis were performed using GE PETtrace cyclotron and GE TRACERlab module (configured for 2- ¹⁸F-fluorodeoxyglucose production), respectively. [¹⁸F] radiofluorination was carried out using dry [¹⁸F] tetrabutylammonium fluoride. Reaction parameters were fine-tuned for optimal radiolabeling. The reaction mixture was purified using neutral alumina. The column was washed with 10% ethanolic-water. [¹⁸F]FMISO was eluted with 5 mL of 10% ethanolic water, followed by [¹⁸F] FET by eluting column with water for injection (WFI) from the column.

Key Results: The difference in polarity of both the radiopharmaceuticals makes it viable to separate in a single synthesis run. [¹⁸F]FMISO being more nonpolar is elutedfirst in 10% ethanol, followed by [¹⁸F]FET using WFI. [¹⁸F]FET and [¹⁸F]FMISO were synthesized with >95% radiochemical and >90% enantiomeric purity with a reliable yield of 10% each.

Research Highlights: [¹⁸F]FET and [¹⁸F]FMISO were successfully synthesized simultaneously using solid-phase extraction purification. Thus, the process is reliable, fast, and economical.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 33:223352 : Preparation and optimization of rhenium-188 4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol with low concentration rhenium-188 radioactivity

Priyanka Singh ¹, Priyanka Gupta ¹, Varsha ¹, Shamim Ahmad Shamim ¹, C S Bal ¹

Aim and Objective: To prepare and optimize rhenium-188 4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (Re-188 HDD)/lipiodol in the in-house radiopharmacy laboratory with low concentration (15–20 mCi/mL) Re-188 radioactivity.

Materials and Methods: Re-188 HDD-conjugated lipiodol was prepared using lyophilized HDD kit and lipiodol. After elution of w-188/Re-188 Generator, 8 ml (120–160 mCi) of Re-188 perrhenate was added to HDD kit along with 1–2 ml of phosphate buffer and kept for boiling in water bath. Aliquots (1 mL) of this sample were collected at different time intervals at 15, 30, 45, 60, 75, 90, 105, and 120 min in different vials and 3 ml lipiodol was added to each vial. Each vial was centrifuged to separate water and lipiodol phase. The lipiodol phase containing lipophilic Re-188 HDD was collected. Quality control test were done and radiochemical purity of radioconjugate was determined by evaluating the radiochromatograms using a TLC scanner. Radiochemical purity of the radioconjugate was checked for all the samples collected at 15, 30, 45, 60, 75, 90, 105, and 120 min of boiling and radiolabeling efficiency was calculated. Stability and shelf life of the final product were also determined.

Result: Percentage radiolabeling efficiency at 15, 30, 45, 60, 75, 90, 105, and 120 min was found to be 4.73, 6.42, 9.77, 31.7, 40.36, 53.94, 21.65, and 6.93, respectively. Re-188-labeled lipiodol was obtained with maximum radiolabeling efficiency of 53.94% at 90 min boiling even when the radioactivity concentration of Re-188 was low; which is similar to the labeling efficiency obtained with highly concentrated Re-188 radioactivity, wherein boiling is done for 60 min. Shelf life of final product was approximately 4 h and good in vitro stability was found.

Conclusion: The preparation procedure of Re-188 HDD/lipiodol with low concentration of Re-188 was optimized, and the highest labeling (53.94%) of Re-188 HDD/lipiodol was obtained at 90 min boiling of Re-188 HDD complex.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 34:094847 : Synthesis and evaluation of novel technetium-99m(CO)₃-fatty acid derivatives prepared via “click chemistry” route as metabolic cardiac tracers

Soumen Das ¹, Anupam Mathur ¹, Navin Sakhare ¹, Vishwas Murhekar ¹, Madhava B Mallia ¹, H D Sarma ², S S Sachdev ¹, A Dash ¹

Introduction: ¹²³ I-Iodophenylpentadecanoic acid (IPPA) is a clinical agent used for detecting metabolic cardiac abnormalities. Due to restricted availability of¹²³ I, there is a continued effort worldwide to develop a technetium-99m (^99mTc) substitute of this agent. The present work employs use of a well-known “click chemistry labeling” approach for incorporating ^99mTc to different fatty acids of variable chain lengths (8, 11, and 15 carbons) and evaluating them for cardiac imaging.

Methods: ω-Bromo fatty acids (8C/11C/15C) were synthetically modified at ω terminal to introduce a triazole ring-bearing glycine moiety in a five-step procedure. These were subsequently radiolabeled with preformed [^99mTc(CO)₃]⁺ synthon (prepared from carbonyl kit) under boiling water condition to yield the desired complexes. Biodistribution studies of the three complexes were performed in normal Swiss mice and results obtained compared with the standard * I-IPPA. Furthermore, in vitro activation of the ^99mTc-labeled tracer by acyl-CoA synthetase was performed to understand the true diagnostic potential.

Results: All the radiolabeled complexes were obtained with radiochemical purities >80% as determined by high-pressure liquid chromatography (HPLC). Biodistribution studies showed myocardial uptake of ~6%–9%ID/g nearly similar to * I-IPPA (~9% ID/g) for all the tracers at 2 min postinjection with significant retention up to 30 min (~1%–2% ID/g) but lower to the standard agent (~7% ID/g). Activation study of 15C fatty acid derivative with acyl-CoA synthetase (determined by HPLC) showed recognition of this complex by the enzyme.

Conclusion: Significant uptake in myocardium and in vitro activation study shows that this “click” approach of ^99mTc incorporation holds potential for myocardial metabolic imaging.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 35:205744 : Evaluation of diagnostic utility of kit-based technetium-99m-HYNIC-RGD for targeting α_vβ₃ integrin receptors in breast cancer patients

Shivani Madaan ¹, Jaya Shukla ¹, Sudipta Chkraborty ¹, Rakhee Vatsa ¹, Priya Bhusari ¹, Dinesh Rawat ¹, B R Mittal ¹

Rationale: Integrin α_vβ₃ plays a critical role in tumor angiogenesis and metastasis. α_vβ₃ integrins are overexpressed in breast carcinoma. Radiolabeled peptides based on the Arg–Gly–Asp (RGD) sequence have high affinity and selectivity for this integrin. The rationale was to establish cost-effective and noninvasive angiogenesis imaging agent with lower radiation burden using technetium-99m (^99mTc).

Methodology: A total of 16 patients (all female patients) of breast cancer before the start of any definitive treatment were enrolled in the study. The lyophilized kit for HYNIC-RGD was incubated with 70 mCi ^99mTcO₄⁻ in water bath at 100°C for 20 min. The preparation was allowed to cool at room temperature for 10 min. Paper chromatography was performed with Whatman strips using saline and acetone as mobile phase. The strips were scanned using radio TLC Scanner; furthermore, the counts were taken in well counter. 20 mCi dose of ^99mTc-HYNIC-RGD was administered to each patient (n=16) through intravenous injection. Planar whole-body scan was acquired after 2 h of dose administration.

Key Results: R_f of ^99mTc-HYNIC-RGD was 0.45 and 0.19 with saline and acetone, respectively. Radiochemical purity was found to be ≥95%. Physiological uptake was seen in nasopharynx, salivary glands, and gastric mucosa. Tracer showed renal excretion. Intense uptake was observed in breast lesions in all patients. Inhomogeneous uptake was also seen in some metastatic sites and lymph nodes.

Research Highlights: ^99mTc HYNIC-RGD can be labeled with high radiolabeling efficiency and may be used as promising single photon emission computed tomography radiopharmaceutical for imaging neo-angiogenesis in breast cancer patients. ^99mTc-HYNIC-RGD reduces the radiation burden to the patient. Tracer is cost-effective as compared to already existing ⁶⁸Ga-RGD.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 36:141332 : Synthesis biological evaluation of technetium-99m-labeled choline derivative as single photon emission computed tomography radioprobe for the assessment of colon cancer tumor

Ambika Parmar Jaswal ¹, Surbhi Prakash ¹, Pallavi Sethi ¹, Harleen Khurana ¹, Baljinder Singh ¹, Anil K Mishra ¹, Puja P Hazari ¹

Background/Aim: Abnormal choline metabolism is a characteristic, associated with oncogenesis and tumor progression. The enhanced choline uptake and phosphorylation in tumor cells has motivated the development of radiolabeled choline derivatives as diagnostic markers for imaging cell membrane proliferation. The goal of this work is preclinical evaluation of choline conjugated to polyamino polycarboxylate chelating agent (diethylene-triamine-pentaacetate acid [DTPA]-bis-choline) radiocomplexed to technetium-99m (^99mTc) for potential tumor imaging applications.

Materials and Methods: The synthesis of DTPA-bis-choline featured quaternization of dimethylaminoethanol with bromoethylamine which act as linker followed by conjugation of highly active primary amine to DTPA anhydride. The derivative was evaluated in-vitro for cell binding, cytotoxicity, tumor kinetics in HCT-116 cell line, whereas in-vivo evaluation in terms of biodistribution, imaging, and toxicity was performed in Balb/c mice and HCT-116 athymic mice models.

Results: The pharmacokinetic studies of ^99mTc-labeled DTPA-bis-choline in mice showed high tumor to background ratio after few minutes of intravenous administration. Stability studies showed that the complex is stable even after 24 h in serum sample. Preclinical findings showed a good visualization of lesions in EAT Balb/C models and HCT-116 athymic mice models with a high target to nontarget ratio.

Conclusion: Preliminary preclinical data suggests ^99mTc-DTPA-bis-choline as a good colon tumor visualizing agent with a high target to non-target ratio.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 37:111334 : Synthesis of generator-based ⁶⁸Ga-labeled DATATOC radiopharmaceutical by an automated module

Rajeev Kumar ¹, Sanjana Ballal ¹, Madhav Yadav ¹, Madhavi Tripathi ¹, N A Damle Chandrasekhar Bal ¹

Rationale: Radiosynthesis of ⁶⁸Ga-DOTANOC has been standardized and used widely worldwide. DATA chelator has been introduced recently, and in continuation to its development in the field of positron emission tomography (PET) imaging agents, the aim of this study was to standardize the synthesis of generator-based 68Ga-labeled DATATOC radiopharmaceutical by an automated module.

Methodology: The reaction vial contained 20 microgram precursor DATATOC dissolved in 1 ml of 0.25 M sodium acetate at pH of 4 with ⁶⁸Ga and was heated at 23°C. After which it was cooled and diluted by adding 3 ml metal-free water, the product was transferred into the t-C-18 cartridge for purification. From this cartridge, product was transferred into product vial with 2 ml, 70% ethanol. Product was passed through 0.22 μm filter. This product was diluted by adding 10 ml normal saline. All synthesis steps were carried out in automated module (Modular Lab, Eckert and Ziegler, Germany). Quality control test (clarity, pH, radiochemical purity) was performed for each synthesis.

Key Results: The average maximum yield of ⁶⁸Ga-DATATOC was 555 MBq (range: 37–1054 MBq) by 1850 MBq ITG generator. ⁶⁸Ga-DATATOC conjugate was prepared with very high radiochemical purity (≈99%). The final ⁶⁸Ga-DATATOC conjugate solution was clear with pH 5.

Research Highlights: ⁶⁸Ga-DATATOC can be synthesized with high radiochemical purity and good stability. The yield of ⁶⁸Ga-DATATOC was high as compared to ⁶⁸Ga-DOTANOC.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 38:131323 : A new, portable solvent extraction-based molybdenum-99/technetium-99m generator utilizing (n, γ) molybdenum-99 in sodium chloride solution for hospital radiopharmacy

Sankha Chattopadhyay ¹, Sujata Saha Das ¹, Madhusmita ¹, Umesh Kumar ¹, Luna Barua ¹, Asit Kumar Pal ¹, Md Nayer Alam ¹, Arup Hudait ¹, Sharmila Banerjee ¹

Rationale: Technetium-99m (^99mTc, t_1/2= 6.02 h; 140.51 keV [89%]) is the most important and useful radioisotope in diagnostic nuclear medicine. The methyl ethyl ketone (MEK)-based solvent extraction technique is a well-known method for the separation of ^99mTc from low specific activity molybdenum-99 (⁹⁹ Mo). Here, we report a new, portable solvent extraction-based⁹⁹ Mo/ ^99mTc generator in tandem with alumina column utilizing (n,γ)⁹⁹ Mo to produce highly purified, concentrated, clinical grade ^99mTc.

Methodology: The pH of the aqueous solution of (n,γ)⁹⁹ Mo (200–500 mCi) in dilute NaOH was adjusted to 7 and saturated with solid NaCl and then transferred to an extraction tube (50 ml) kept in the lead shielded arrangement. The pertechnetate (^99mTcO₄⁻) was selectively extracted in MEK and passed through two small alumina column (neutral alumina and acidic alumina). Finally, highly pure ^99mTc was recovered from acidic alumina column with 3–5 ml saline in high concentration. The performance of this new⁹⁹ Mo/ ^99mTc generator was evaluated by studying the recovery yield of ^99mTc, physicochemical tests, and radiolabeling with Tc cold kits such as methylene diphosphonate (MDP), diethylene-triamine-pentaacetate acid (DTPA) and sestamibi (MIBI).

Key Results: The average yield of separation of ^99mTc was above 90% and⁹⁹ Mo breakthrough in ^99mTc pertechnetate was <0.0002% (n = 10). The final ^99mTcO₄⁻ fraction has the Mo and Al content <10 ppm and MEK content <0.1% v/v, with radiochemical (RC) purity >99% and radionuclidic (RN) purity >99.9%. The efficacy of labeling specific compounds was assessed using standard radiopharmaceutical kits, such as ^99mTc-MDP, ^99mTc-DTPA, and ^99mTc-MIBI, and RC purity was above 95% (n = 6).

Research Highlights: The newly developed portable⁹⁹ Mo/ ^99mTc generator can provide the highly concentrated and purified ^99mTc-pertechnetate using low specific activity⁹⁹ Mo and finds its application for hospital radiopharmacy.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 39: 123259 : Technetium-99m HYNIC-TOC for somatostatin receptor expression: A single-center experience

R Vishnukumar ¹, M S Bharadwaj ¹, P A Meivel ¹, H Dhanapathi ¹, Nandini Pandit ¹, Madhusudhanan Ponnusamy ¹

Introduction: Somatostatin receptor overexpression is seen in many tumors such as neuroendocrine tumors (NETs), medullary carcinoma of thyroid, neuroblastoma, and pheochromocytoma. Various single photon emission computed tomography and positron emission tomography tracers are available for evaluation of such tumors. Utility and usefulness of these tracers vary based on they affinity toward to receptors. Technetium-99m (Tc-99m)-labeled HYNIC-TOC has the advantage of being used in most centers with gamma camera. In this study, we evaluated the usefulness of Tc-99m HYNIC-TOC scintigraphy in the diagnosis of various tumors.

Aim and Objectives: To evaluate the usefulness of Tc-99m of HYNIC-TOC scintigraphy in the diagnosis of various tumors in patients referred to the Department of Nuclear Medicine, JIPMER.

Materials and Methods: We retrospectively evaluated Tc-99m HYNIC-TOC scans done for patients during the period between January 2015 and July 2017. Demographic data, clinical history, biopsy reports, surgical details, and scan features were tabulated and analyzed.

Results: A total of 34 scans were analyzed. The distribution is as follows: suspected NETs – 24, suspected tumor-induced osteomalacia - 4, meningioma – 4, neuroblastoma and follicular variant of papillary carcinoma of thyroid – 1 each. Among these, 23 scans (67.64%) were positive and 11 (32.35%) were negative. Among the patients with suspected NET, 17 (70.83%) were scan positive and 7 (29.16%) were scan negative. Three out of five pancreatic NET were negative on scan. Histopathology reports were available for 17 cases – all of the reports were positive for malignancy. Fourteen of histopathologically positive patients (82.3%) had uptake on HYNIC-TOC scan, while 3 (17.64%) did not show any significant uptake.

Conclusion: Out of 34 patients who had undergone Tc-99m HYNIC-TOC scans, 67.64% of the scans were positive. Sensitivity of HYNIC-TOC scan in this study group was found to be 82.3%. Tc-99m HYNIC-TOC is a cost-effective study that can be done in centers with only gamma camera for evaluation of tumors with somatostatin receptor expression.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Oncology and Metabolic: OP 40:113819: Technetium-99m-prostate-specific membrane antigen-11: Single photon emission computed tomography imaging agent for prostate cancers

Kusum Vats ¹, Rohit Sharma ¹, Haladhar Dev Sarma ¹, Drishty Satpati ¹, Ashutosh Dash ¹

Rationale: Prostate-specific membrane antigen (PSMA) being over-expressed in primary prostate tumors and related metastatic sites is an interesting biomarker for staging and follow-up of prostate cancers. PSMA-11 has been established as a PSMA-selective ligand and ⁶⁸Ga-PSMA-11 is a clinically accepted positron emission tomography (PET) imaging agent for prostate cancer. The N, N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N, N′-diacetic acid chelator conjugated to PSMA targeting moiety in PSMA-11 ligand has nitrogen and oxygen donors that are capable of coordinating with technetium-99m (^99mTc). Hence, in this study, we investigated the suitability of ^99mTc-labeling of PSMA-11 and its potential as SPECT probe for prostate cancer imaging.

Methodology: ^99mTc-labeling of PSMA-11 was conducted by adding PSMA-11 (45 μg) to ^99mTcO₄⁻ (370 MBq) followed by SnCl₂(25 μg) and heating in a boiling water bath for 20 min. Radiochemical yield and purity of ^99mTc-PSMA-11 was determined by thin-layer chromatography (TLC) and reverse phase high-performance liquid chromatography (HPLC). In vitro evaluation was carried out in PSMA-positive LNCaP cells. Pharmacokinetics was evaluated by performing biodistribution studies in normal Swiss mice at 30 min, 1 h, and 3 h p.i.

Key Results: The amount of ^99mTc-colloid was determined by TLC in acetonitrile/water (1:1, v/v) where R_f(colloid) = 0, R_f(^99mTcO₄^-) = 1, R_f(^99mTc-PSMA-11) = 1. To distinguish between ^99mTcO₄^- and ^99mTc-PSMA-11, MEK was used as the mobile phase; R_f(^99mTcO₄^-) = 1, R_f(^99mTc-PSMA-11) = 0. The radiochemical yield of ^99mTc-PSMA-11 was ~50% as determined by paper chromatography. The log P value (−2.1 ± 0.14) indicated hydrophilic character of the radiotracer. ^99mTc-PSMA-11 exhibited 15% binding to LNCaP cells. Biodistribution studies revealed rapid urinary excretion (53.50% ± 8.11% at 3 h p.i.) and fast clearance from other nontarget organs (blood, lungs, liver, and intestine).

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 41:105434 : ¹⁶⁶ Ho-labeled microspheres for radioembolic therapy of hepatocellular carcinoma

Suresh Subramanian ¹, K V Vimalnath ¹, Ashutosh Dash ¹

Rationale: Radioembolization with suitable therapeutic isotopes is an effective targeted therapy for hepatocellular carcinoma (HCC), but there is a need for suitable indigenously prepared alternative to imported therapeutic microspheres in this application.¹⁶⁶ Ho can be produced in the reactor and has favorable emission characteristics (T_1/2= 26.8 h, E_βmax= 1.84 MeV, E_γ= 81 keV) for HCC therapy. It is proposed to tag indigenously produced¹⁶⁶ Ho to commercially available resin microspheres and evaluate the radiolabeled product physicochemically and biologically for its suitability toward the intended application.

Methodology:¹⁶⁶ Ho was produced by (n,γ) irradiation of¹⁶⁵ Ho (as Ho₂O₃) target in Dhruva reactor and processed to give¹⁶⁶ Ho as HoCl₃. Different commercial resin microspheres (Biorex™ 70, Biorex™ 5, Biorex AG® 50W) were tested for¹⁶⁶ Ho-labeling. Optimized formulation of the best-yielding¹⁶⁶ Ho-labeled microsphere was checked for in vitro stability in saline and serum. In vivo distribution and retention of the formulation was tested using our previously reported protocol in Wistar Rat model.

Key Results:¹⁶⁶ Ho was produced with good specific activity (>13G Bq/mg). Using the optimized protocol, Biorex™ 70 was labeled with¹⁶⁶ Ho with >90% yield at pH 8.5. The labeling was stable (>95%) in both saline (pH 7.0) and serum for up to 72h postpreparation. In vivo studies showed >90% retention of¹⁶⁶ Ho activity in the liver at 72 h postinjection with minimal leakage to nonspecific organs.

Research Highlights: Preparation and preliminary evaluation of¹⁶⁶ Ho-labeled microspheres indicates a potentially viable indigenous alternative to imported radioactive microspheres for treatment of HCC.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 42:142436 : Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in recurrent anorectal melanoma

Ajinkya N Bakare ¹, Archi Agrawal ¹, Avinash Saklani ¹, Sneha Shah ¹, Nilendu Purandare ¹, Archi Agrawal ¹, Ameya Puranik ¹, Venkatesh Rangarajan ¹

Rationale: To evaluate diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG-PET/CT) in anorectal melanoma with suspected recurrence after surgical resection.

Methodology: This was a retrospective observational study; patients with clinical or radiological suspicion of disease recurrence referred for PET/CT from January 2006 to December 2016 were included in the study. Diagnostic performance of PET/CT was evaluated for disease recurrence. Any area with intensity greater than background that could not be identified as physiological activity on PET images or which on CT correlation did not fit into benign (infective/inflammatory/degenerative) was considered to be suggestive of tumor on the PET study. PET/CT findings were correlated with histopathology results. When tissue diagnosis was not available, clinical or radiological follow-up was used as reference standard.

Key Results: A total of 24 patients were included. All the patients were treated previously by surgery, radiotherapy, or chemotherapy. PET/CT detected disease recurrence in 20 patients (83.3%). Ten patients had recurrence at the primary site, two of whom also had distant metastases, and two had only loco-regional metastatic nodes. In remaining 10 patients, there was no primary site recurrence; however, two patients had loco-regional nodal and distant metastases while two patients had only distant metastases. Histopathological confirmation was available in six patients whereas imaging and clinical follow-up confirmed recurrence in remaining patients. PET/CT was negative for recurrence in three patients. PET/CT was false negative in one patient which missed liver metastasis. Sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT was found to be 95%, 100%, 100%, and 75%, respectively, with accuracy of 96%.

Research Highlights: FDG PET/CT shows high diagnostic accuracy in detection of recurrent disease in anorectal melanoma.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 43:165403 : Prognostic significance of nodal disease on baseline fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of cervix

Ambalika Veer ¹, Sneha Shah ¹, Nilendu Purandare ¹, Archi Agrawal ¹, Ameya Puranik ¹, Venkatesh Rangarajan ¹

Rationale: Metastatic nodal disease is negative prognostic factor in carcinoma cervix. Cross-sectional imaging is used to assess local as well as metastatic disease extent for optimal treatment planning. We aim to study prognostic value of nodal metabolic parameters on staging fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) (PET) in carcinoma cervix.

Methodology: This was single-center institutional ethics committee-approved retrospective study. A total of 57 consecutive patients during 2005–2009, who had undergone baseline PET and treated with curative chemoradiation, were included in the study. Nodes with FDG uptake more than blood-pool were considered positive. Metabolic parameters maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total glycolysis index (TLG) were calculated for the nodal disease. Cutoff for SUVmax, SUVmean, MTV, and TLG were calculated using receiver operating characteristic analysis. Kaplan–Meir analysis using log-rank method was used for survival analysis. P < 0.05 was considered significant.

Key Results: Median follow-up was 99 months (5–140). Thirty-one patients had pelvic while 11 had pelvic and para-aortic nodal metastases. Fifteen patients did not have nodal metastases. Twenty-two patients had events (progression or relapse). Patients with nodal disease had poorer event-free survival than those with no nodal disease (76 vs. 133 months) (p value 0.004). In univariate analysis, SUVmax, SUVmean, MTV, and TLG of nodal disease correlated with the event-free survival with P = 0.008, 0.03, 0.04, and 0.01, respectively.

Research Highlights: In baseline FDG PET CT of cervical cancer patients, metabolic parameters of nodal disease show strong inverse correlation with event-free survival.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 44:041644 : Preclinical development of CD38-targeted [89Zr]Zr-DFO-daratumumab for imaging multiple myeloma

Anchal Ghai ¹, Dolonchampa Maji ^1,², Nicholas Cho ^1,², Chantiya Chanswangphuwana ³, Michael Rettig ³, John DiPersio ³, Walter Akers ⁴, Farrokh Dehdashti ¹, Samuel Achilefu ^1,^2,⁵, Ravi Vij ³, Monica Shokeen ^1,²

Rationale: Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. CD38 is a type II transmembrane glycoprotein over-expressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is an FDA-approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [89Zr]Zr-DFO-daratumumab positron emission tomography/computed tomography imaging in MM tumor models.

Methodology: Daratumumab was conjugated to DFO-Bz-NCS for radiolabeling with⁸⁹ Zr. Chelator conjugation was confirmed by electrospray ionization-mass spectrometry, and radiolabeling was monitored by ITLC. Cellular studies using CD38⁺ human myeloma MM1.S-luciferase (MM1.S) cells determined the affinity, immunoreactivity, and specificity of [89Zr]Zr-DFO-daratumumab. CD38^low 5TGM1-luciferase (5TGM1) murine MM cells served as negative controls. [89Zr]Zr-DFO-daratumumab PET/CT small animal imaging was performed in SCID mice-bearing solid and disseminated MM tumors. Tissue biodistribution (7 days after tracer administration, 1.11 MBq/animal, n = 4–6/group) was performed in wild-type and MM1. S tumor-bearing SCID mice.

Key Results: Specific activity of 55.5 MBq/nmol (0.37 MBq/μg) was reproducibly obtained with⁸⁹ Zr-daratumumab-DFO. Flow cytometry confirmed CD38 expression (>99%) on the surface of MM1.S cells. A dissociation constant, K_d: 3.3 nM (± 0.58) and receptor density, B_max: 10.1 fmol/mg (±0.64) were obtained with saturation binding assay. [89Zr]Zr-DFO-daratumumab/PET demonstrated specificity and sensitivity for detecting CD38⁺ myeloma tumors of variable sizes (8.5–128 mm³). Discrete medullar lesions, confirmed by bioluminescence images, were efficiently imaged with [89Zr]Zr-DFO-daratumumab/PET. Biodistribution at 7 days postadministration of [89Zr]Zr-DFO-daratumumab showed prominent tumor uptake (27.7% ± 7.6% ID/g).

Research Highlights: [89Zr]Zr-DFO and Cy5-daratumumab demonstrated superb binding to CD38⁺ human MM cells and significantly low binding to CD38^low MM cells. Daratumumab bio-conjugates are being evaluated for image-guided delivery of therapeutic radionuclides.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 45:180058: ¹⁸F-fluorodeoxyglucose and ⁶⁸Ga-DOTANOC positron emission tomography-computed tomography in Von Hippel–Lindau syndrome

Shamim A Shamim ¹, Arun Prashanth ¹, Konudula Sreenivasa Reddy ¹, C S Bal ¹

Introduction: Von Hippel-Lindau (VHL) syndrome is an autosomal dominant neoplastic disorder with the propensity to develop multiple benign and malignant tumors. VHL hemangioblastomas (VHL-HB) have multiple SSTR subtypes that can be exploited for scanning. Fluorodeoxyglucose (FDG) uptake is seen in the poorly differentiated tumors of VHL.

Aim: To use ¹⁸F-FDG and ⁶⁸Ga-DOTANOC positron emission tomography-computed tomography (PET-CT) for patients with VHL for maximum detectability of lesions.

Materials and Methods: ¹⁸F-FDG and ⁶⁸Ga-DOTANOC PET-CT scans were done on proven VHL patients. A total of eight scans were performed on six patients (two patients had both ¹⁸F-FDG and ⁶⁸Ga-DOTANOC PET-CT done). The indications of scan were to evaluate for the sites of involvement or restage the patients after surgery.

Results: Of the six patients, three had cerebellar hemangioblastomas, one had retinal angiomas. Five had adrenal lesions out of which two were operated upon. Of six patients, four had pancreatic lesions. Three patients were found to have RCC, one had spinal hemangioblastoma. One had papillary cystadenoma of epididymis. HBs (five locations including brain, spinal cord, and eye) and neuroendocrine tumors (seven including pancreas and adrenal) of VHL show uptake in ⁶⁸Ga-DOTANOC PET-CT whereas renal neoplasm (1) and metastasis (1) show uptake in FDG PET-CT. Pancreatic and adrenal neoplasm have equal propensity for uptake in both the scans.

Conclusion: Both ¹⁸F-FDG and ⁶⁸Ga-DOTANOC PET-CT act as complimentary imaging modalities for diagnosis of various tumors in VHL.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 46:225508 : Correlation of bone marrow involvement using fluorodeoxyglucose positron emission tomography-computed tomography and bone marrow biopsy in diagnosis of lymphomas

Dharmesh Paliwal ¹, M S Chauhan ¹, Braj Kishore Singh ¹

Purpose: The evaluation of bone marrow infiltration (BMI) is of crucial importance in the staging of lymphoma. Although bone marrow biopsy (BMB) is the reference standard for the evaluation of BMI, it has limitations. Positron emission tomography/computed tomography (PET/CT) has become an excellent tool in staging of lymphoma, and bone marrow uptake is correlated with the involvement of lymphoma. The aim of this study was to assess the utility of PET/CT and its concordance with BMB in the detection of BMI in patients with lymphomas.

Patients and Methods: One hundred and five patients with Hodgkin's lymphoma (70) and non-Hodgkin's lymphoma (35) were referred for a PET/CT and a BMB at the initial staging. The reference standard was BMB.

Results: BMI was detected by PET/CT in 29 (27%) and by BMB in 27 (25%) cases. There was concordance between PET/CT and BMB in 77 patients (73%) - 14 with positive PET/CT and BMB results and 63 with negative PET/CT and BMB results. Discordant results were observed in 28 patients (26%) - 15 of them with positive PET/CT and negative standard BMB results (not performed in active sites) and 13 of them have bone marrow biopsy positive and negative PET scan. The sensitivity, specificity, accuracy, as well as positive and negative predictive values of FDG-PET/CT for the detection of BMI were 52%, 80%, 48%, 83%, and 73%, respectively.

Conclusions: FDG PET/CT has good concordance with BMB, especially in cases of Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma, which makes it a complementary technique. It also helps select the biopsy site in cases with negative results.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 47:202959 : Quality of life assessment following lutetium-177-DOTANOC therapy in inoperable and metastatic neuroendocrine tumors

Deepanksha Datta ¹, Narvesh Kumar ¹, P K Pradhan ¹, S Gambhir ¹

Rationale: Peptide receptor radionuclide therapy (PRRT) is a promising tumor-directed systemic treatment for metastatic/inoperable well-differentiated neuroendocrine tumors (NETs). We evaluated the quality of life (QoL) assessment following lutetium-177 (Lu-177) DOTANOC therapy in this patient subset.

Methodology: One to four cycles of Lu-177 DOTANOC therapy (150–200 mCi) was administered as per the EANM guidelines to patients of well-differentiated metastatic/inoperable NET. QoL was assessed with EORTC QLQ-C30 (Version 3) before and after each cycle of PRRT. Median QoL scores at baseline and after each cycle were compared and the various QoL scores were correlated with Karnofsky performance score (KPS) after each cycle.

Results: A total of 13 patients were included with a mean age of 54 years and 10 (77%) were males. All patients took at least 1 cycle, seven took 2 cycles, four took 3 cycles, and two took all 4 cycles of PRRT. Mean interval between each therapy was 3 months (2–4 months). Significant improvement was noted only in the global health score, after 2 cycles of PRRT. No significant correlation was noted in QoL scores and KPS after each cycle. Of 13 patients, seven died during the course of therapy.

Research Highlights: Lu-177 DOTANOC therapy improved the global QoL in patients with metastasized neuroendocrine tumors, after 2 cycles of the therapy. No significant change in the functional, symptom scales or KPSs was noted.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 48:174931 : Evidence of prostate-specific membrane antigen expression in metastatic differentiated thyroid cancer using ⁶⁸Ga prostate-specific membrane antigen-N, N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N, N′-diacetic acid positron emission tomography/computed tomography

Priyanka Verma ¹, Gaurav Malhotra ¹, Vilas Meshram ¹, Ritesh Agrawal ¹, Sunita Sonavane ¹, Ramesh V Asopa ¹

Rationale: Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase that is not only expressed in prostate cancers but also in small intestine, renal tubules, salivary glands, and tumor neovasculature. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory cancers probably due to its expression in microvessels of these tumors. However, systematic studies exploring PSMA uptake in thyroid tumors are lacking. Therefore, we undertook this pilot study to assess PSMA expression in patients with metastatic differentiated thyroid cancer (mDTC).

Methodology: Ten patients of mDTC (5 males; age range 38–65 years; mean age 50 years) (8 iodine-avid and 2 thyroglobulin elevation/negative iodine scintigraphy [TENIS] cases) underwent Ga-68 PSMA-N, N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N, N′-diacetic acid HBED-CC positron emission tomography/computed tomography (PET/CT) as per the institution protocol. PSMA expression (maximum standardized uptake value [SUVmax]) in the primary and metastatic lesions was compared with 18F-fluorodeoxyglucose and 131-iodine scan findings.

Key Results: In seven of eight patients with iodine avid disease, multiple sites of metastatic disease showed PSMA uptake. PSMA PET/CT detected 30/32 total lesions (93.75%))SUVmax ranging from 4.86 to 101.81 with median SUVmax of 31.35) while FDG PET/CT was positive in 23/32 lesions (81.85%). Of 30 lesions, 21 (70%) lesions that showed PSMA expression were localized to the bones. PSMA localized a lesion in each of the 2 TENIS patients similar to FDG PET scan.

Research Highlights: This pilot study results indicate that 68 Ga PSMA PET/CT demonstrates PSMA uptake in metastatic DTC with most (70%) of PSMA mets being localized to the bones. 68Ga PSMA PET/CT could be useful for the identification of patients who might qualify for PSMA-targeted radionuclide therapy opening a new potential treatment modality for DTC.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 49:103607 : Ga-68-labeled erlotinib: Novel positron emission tomography probes for imaging epidermal growth factor receptor over-expressing tumors

Akanksha Jain ^1,², Mythili Kameswaran ¹, Usha Pandey ^1,², Kumar Prabhash ³, Haladhar Dev Sarma ⁴, Ashutosh Dash ^1,²

Rationale: Molecular imaging using radiolabeled tyrosine kinase inhibitors (TKIs) is an attractive strategy for detection of epidermal growth factor receptor (EGFR)-positive tumors.^[1],[2],[3] Two analogs of one such TKI, erlotinib, were synthesized for PET imaging by derivatizing the parent erlotinib molecule for conjugation with p-SCN-Bn-NOTA and p-SCN-Bn-NODAGA toward ⁶⁸Ga labeling.

Methodology: NOTA-erlotinib and NODAGA-erlotinib conjugates were synthesized and radiolabeled with Ga-68. Cell-binding studies were carried in EGFR-positive A431 cells. Biodistribution studies of ⁶⁸Ga-NOTA-erlotinib were carried in EGFR-positive tumor-bearing SCID mice and that of ⁶⁸Ga-NODAGA-erlotinib were performed in Swiss mice.

Key Results: The bifunctional chelator-erlotinib conjugates were radiolabeled with Ga-68 in ≥95% yields. The log P values of ⁶⁸Ga-NOTA-erlotinib and ⁶⁸Ga-NODAGA-erlotinib were −0.6 ± 0.1 and −1.21 ± 0.2, respectively. ⁶⁸Ga-NOTA-erlotinib showed an uptake of 9.8% ± 0.4% in A431 cells which reduced by 55.1% ± 0.2% with 10 μg of cold erlotinib. ⁶⁸Ga-NODAGA-erlotinib showed a binding of 7.8% ± 1.3% in A431 cells and an inhibition of 30.7 ± 0.5%. ⁶⁸Ga-NOTA-erlotinib showed moderate tumor accumulation (1.5% ± 0.1% ID/g at 30 min p.i.; 0.7% ± 0.2% ID/g at 1 h p.i.) in SCID mice-bearing tumor. ⁶⁸Ga-NODAGA-erlotinib exhibited faster clearance of activity from the organs in Swiss mice as compared to ⁶⁸Ga-NOTA-erlotinib.

Research Highlights: Novel Ga-68 labeled erlotinib analogs were synthesized which showed specificity to EGFR-positive A431 cells, ⁶⁸Ga-NOTA-erlotinib being superior to ⁶⁸Ga-NODAGA-erlotinib. ⁶⁸Ga-NOTA-erlotinib also had moderate tumor uptake while ⁶⁸Ga-NODGA-erlotinib demonstrated faster clearance from nontarget organs of normal Swiss mice. The results of our study show that the ⁶⁸Ga-BFC-erlotinib conjugates merit further exploration.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 50:230514 : Comparison of response assessment following radioactive iodine therapies in micro-metastases versus macro-nodular pulmonary metastases of papillary thyroid carcinoma

Saumya Sara Sunny ¹, Julie Hephzibah ¹, David Mathew ¹, Nylla Shanthly ¹, Regi Oommen ¹

Rationale: Pulmonary metastases in papillary thyroid carcinoma (PTC) have two common presentations, micro-metastases (M) and macro-nodular metastases (N). The mainstay of treatment, posttotal thyroidectomy, is multiple radio-iodine ablations (RAIAs) every 6–12 months for lesions that concentrate radio-iodine. Response assessment is determined by decline in serum thyroglobulin (Tg) levels, disease regression on chest X-ray (CXR) and whole-body iodine scintigraphy (TWBS). This study aims at assessing the difference in response to RAIA.

Methodology: Retrospective analysis of PTC patients who visited the outpatient department from January 2008 to July 2017 was done. Patients with pulmonary metastases treated with RAIA and a minimum follow-up of 8 months were included. The initial and the final Tg, TWBS, and CXR were analyzed for both groups. Final outcome in terms of complete response, disease regression, static disease, and disease progression was determined.

Key Results: A total of 71 patients fulfilled the inclusion criteria – 43 females and 28 males. The median age was 39 years and the range was 14–79 years. 45 (63.3%) had M and 26 (36.6%) had N disease. The average number of therapies was 3 and maximum follow-up period was 15 years. Of the 45 M patients, 1 had progression, 7 were static, 23 had regression, and 14 had complete response. Of the 26 N patients, 22 had progression, 2 were static, 1 had regression, and 1 had complete response.

Research Highlights: Those with micro-metastases respond to RAIA with a better outcome when compared to those with macro-nodular metastases.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 51:230532 : Evaluation of renal function with technetium-99m diethylene-triamine-pentaacetate acid scintigraphy in patients with beta-thalassemia

Subha Shankar Das ¹, Shwetal Pawar ¹, Bhairavi Bhatt ¹

Objective: A pilot study was conducted with technetium-99m diethylene-triamine-pentaacetate acid (Tc-99m DTPA) renal scintigraphy in beta-thalassemia patients with serum creatinine within normal range to evaluate any derangement in renal function parameters.

Materials and Methods: The study was conducted in thirty patients with beta-thalassemia major and intermedia, with serum creatinine within normal range, raised serum ferritin level and on tablet deferasirox. The mean age was 11.5 ± 6.5 years. DTPA renal scans were performed on Siemen's dual head gamma camera. The patients were injected Tc-99m DTPA (mean dose = 0.05 mCi/kg) without using diuretic and immediate dynamic images were acquired in posterior projection for 20 min. Statistical analysis was done using Chi-square test for determining the significance of measured GFR, time to peak, and transit time in thalassemia major and intermedia groups.

Results: In the major and intermedia groups, 100% and 85.7% of the patients showed reduction in the measured glomerular filtration rate (GFR) from minimum normal estimated GFR (based on CKD-EPI study, KDIGO trial, and MDRD study equation) for age (90 ml/min for age 2–12 years and 100 ml/min for age 3–21 years), respectively, which was statistically insignificant (P = 0.534). The peak uptake was delayed in 22.2% in single as well as both kidneys in intermedia group and 9.5% in single as well as both kidneys in major group, which statistically showed significance (P = 0.354). The transit time was prolonged in 11.1% and 44.4% in single and both kidneys, respectively, in intermedia group and 4.8% and 11.9% in single and both kidneys, respectively, in major group, which statistically showed significance (P = 0.24).

Conclusion: This study demonstrates early renal dysfunction as seen by statistically significant delay in time to peak and prolongation of the transit time in patients with beta-thalassemia with serum creatinine within normal range. However, the GFR did not show statistically significant reduction.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 52:211121 : Technetium-99m-mebrofenin hepatobiliary scintigraphy with single photon emission computed tomography-computed tomography to assess total and segmental liver function and to predict future liver remnant functional volume after liver resection

Suneetha Batchu ¹, Y Raghavendra Babu ¹, Tarun Piplani ², Dheeraj Guatam ³, AS Soin ¹

Rationale: Preoperative evaluation of liver quality and future liver remnant (FLR) function is vital for liver resection (LR). Computed tomography (CT) volumetry does not provide information on functional capacity. The aim was to evaluate value of hepatobiliary scintigraphy (HBS) with technetium-99m-mebrofenin.

Methodology: Liver functional capacity expressed as mebrofenin uptake rate (MUR) in %/min/sq. m and correlated with histology and CT volumetry. Total liver function (TLF), posthepatectomy liver failure (PHLF), and mortality after LR were analyzed.

Key Results: HBS performed in 9 healthy volunteers and 40 patients; all patients had liver biopsy. TLF-MUR and blood pool clearance in Group A (normal liver function), Group B (impaired function), and Group C (severely impaired function) patients were significantly different (P = 0.000) [Table 1]. In Group B, TLF-MUR was similar among patients with mild cholestasis, moderate steatosis, and fibrotic livers. Out of 40, five had low TLF-MUR (chronic liver disease) with no liver space occupying lesion (SOL). Of the 35 patients with SOL, 24 underwent LR (>2 segments), and 11 could not - 3 due to oncological reasons and 8 due to low FLR-MUR with high portal pressures. Of the latter 8, liver transplant (LT) was done in 5 and 3 are awaiting LT. In the LR group (n = 24), 22 had no morbidity or mortality. In these, FLR-MUR was between 2.9%/min/sq.m to 7.97%/min/sq.m, while FLR volume on CT was between 38.8% and 92%. Two of these 22 needed preoperative portal vein embolization (PVE) to augment FLR-MUR. After LR, 2/24 patients developed PHLF and died. Their FLR-MUR and FLR CT volumes were 0.4%/min/sq.m, 2.8%/min/sq.m and 38%, 50.2%, respectively.

Table 1.

graphic file with name IJNM-32-2-g001.jpg

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Research Highlights: Preresection HBS is valuable in predicting overall liver quality and functional liver remnant and risk of PHLF even among those with acceptable remnant volume. Patients with adequate FLR CT volume but decreased FLR-MUR may benefit from PVE.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 53:101810 : Gastrin-releasing peptide receptor-targeted ⁶⁸Ga-molecular probes for prostate cancer imaging

Drishty Satpati ¹, Rohit Sharma ¹, Ashutosh Dash ¹

Rationale: The elevated expression levels of gastrin-releasing peptide receptors (GRPRs) in prostate tumors have garnered attention toward the development of GRPR-targeted radiopeptides. Bombesin analogs have high affinity toward GRPR receptors; hence, radiolabeled bombesin derivatives are being developed as specific radiotracers for imaging and therapy of GRPR-positive prostate cancers. The better clearance and targeting properties of GRPR antagonist peptides has led to evolution of the radiotracer, ⁶⁸Ga-RM2 which is now in clinical trials. We have evaluated HBED-CC variants of GRPR antagonist peptides, RM2 and RM26.

Methodology: The antagonist peptides DOTA-RM2/HBED-CC-RM2 (RM2: 4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH₂) and NODAGA-PEG₂-RM26/HBED-CC-PEG₂-RM26 (RM26: PEG₂-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH₂) were synthesized using standard Fmoc chemistry. The purified peptide conjugates were radiolabeled with ⁶⁸Ga. The radiotracers have been evaluated for their specificity toward prostate carcinoma PC-3 cells.

Results: RM2, HRM2, RM26, and HRM26 were synthesized in >99% purity. The pure peptide-conjugates were radiolabeled with ⁶⁸Ga in high specific activity (10 GBq/μmol) and radiochemical yield (>97%). The HBED-CC variants were observed to less hydrophilic than their DOTA or NODAGA counterparts. However, all the ⁶⁸Ga-labeled GRPR antagonist peptides exhibited high specificity toward PC-3 cells.

Conclusion: ⁶⁸Ga-labeled GRPR antagonist peptides have the potential for being developed as prostate cancer imaging agents.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Infection and Inflammation: OP 54:221643 : Acetamidobenzoxazolone-based positron emission tomography and single photon emission computed tomography imaging probes for targeting translocator protein in inflammatory conditions

Neelam Kumari ^1,², Ankur Kaul ¹, Sunita Bhagat ², Anjani K Tiwari ¹

Rationale: Inflammation is the prime pathophysiological response of the body and the quantification of inflammation biomarkers will help in determining the severity and the region of a pathological attack or injury. Translocator protein (TSPO) is one of the inflammation biomarkers whose overexpression can be quantified by employing various imaging modalities. Hence, we have synthesized¹¹ C-labeled positron emission tomography (PET) imaging probe-[¹¹ C]MNBP for targeting TSPO overexpression in brain and ^99mTc-labeled macrocycles conjugated with TSPO ligand-[^99mTc]MPAOT for targeting TSPO overexpression in peripheral organs.

Methodology: After in-silico screening, [¹¹ C]MNBP and [^99mTc]MPAOT were synthesized in high overall yield by following the convergent methodology of six and nine synthetic steps. The biological evaluation of [¹¹ C]MNBP through PET imaging has been done on ischemic rat brain model, and for [^99mTc]MPAOT, SPECT imaging was performed on lung inflammation mice model.

Key Results: The obtained Gleason's score from CADD studies signifies the efficient binding potential of the designed ligands. Characterization and validation of all synthesized compounds were done with different spectroscopic techniques (nuclear magnetic resonance, Fourier-transform infrared, and high-resolution mass spectrometry). PET imaging and in vitro autoradiography studies carried out in rat model showed the higher accumulation of radiolabeled drug [¹¹ C]MNBP in ischemic/inflamed region in comparison to the nonischemic region. The specificity and selectivity of the ligand have also been proved in displacement experiments by using PK11195 and MNBP as a cold substitute. In case of SPECT imaging, [^99mTc]MPAOT also reflected higher accumulation of radioactivity in inflammated lungs in comparison to the control and specificity has been proved in blocking experiment by using PK11195 as blocking agent.

Research Highlights: The present data show that ^99mTc-MPAOT acts as a potential SPECT imaging marker for TSPO targeting in peripheral organs and [¹¹ C]MNBP acts as a potential PET probe for targeting TSPO in brain.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 55:134023 : In vitro uptake/binding study of ⁶⁸Ga-labeled DOTA-GF-17 with Gram-positive and Gram-negative bacterial strains

Shalini Chopra ¹, Anil K Mishra ¹, Hans-Jürgen Wester ², Baljinder Singh

Rationale: GF-17 is an antimicrobial peptide fragment active against both Gram-positive and Gram-negative bacteria. Previously, we have done preclinical evaluation of ⁶⁸Ga-labeled DOTA-GF-17 to develop it as a potential positron emission tomography (PET) imaging agent against bacterial infections. In the present study, we have evaluated the affinity of ⁶⁸Ga-DOTA-GF-17 for Gram-positive and Gram-negative bacterial strains.

Methodology: GF-17 was synthesized by solid phase peptide synthesis and coupled with DOTA in solution phase. Purification and characterization were done by high pressure liquid chromatography and mass spectroscopy. DOTA-GF-17 (20.0 μL; 1 mmol/mL) was radiolabeled with ⁶⁸Ga at pH 4 (adjusted with sodium acetate buffer) by heating at 95°C for 25.0 min. Radiolabeled product was purified by using C8 SPE cartridge and quality control tests were performed. For the uptake/binding studies, live and heat-killed strains of Staphylococcus aureus and Pseudomonas aeruginosa (2 × 10⁷ CFU) (suspended in 200 μL of PBS) were incubated with ⁶⁸Ga-DOTA-GF-17 (200 μCi) at 37°C for different time intervals.

Key Results: The mass spectroscopy analysis demonstrated that the molecular mass of DOTA-GF-17 was 2487.2. The radiolabeling efficiency, plasma protein binding, and lipophilicity for ⁶⁸Ga-DOTA-GF-17 were 95.0% (stable for up to 3 h), 80.98%, and −3.12, respectively. The maximum uptake binding of ⁶⁸Ga-DOTA-GF-17 was observed in live and heat-killed S. aureus with values 69.08% (120 min postincubation) and 78.34% (30 min postincubation). Comparatively, lower uptake binding was observed in live and heat-killed P. aeruginosa with values 32.56% (30 min) and 43.94% (30 min), respectively.

Research Highlights: A successful radiolabeling of ⁶⁸Ga with GF-17 was achieved. Uptake/binding studies showed higher uptake of ⁶⁸Ga-DOTA-GF-17 in case of S. aureus. Due to higher binding with Gram-positive bacteria, this radiolabeled peptide conjugate can be seen as potential imaging probe for detecting Gram-positive bacterial infections.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 56:211242 : Evaluation of viability of microorganisms in ⁶⁸Ga-, ¹⁸F-, ^99mTc-, and ¹⁷⁷Lu- labeled radiopharmaceuticals

Arpit Mitra ¹, Sangita Lad ², Sharmila Banerjee ^1,², Savita Kulkarni ²

Rationale: Parametric release and retrospective sterility test of various diagnostic and therapeutic radiopharmaceuticals (RPs) make it essential to rule out false negative results due to inhibition of microorganisms (MOs) mediated by ionizing radiations emitted from RPs. This study is designed to evaluate the viability of positive control MOs used in sterility test in the presence of RPs and to observe whether viability depends on ionizing radiations or chemical constituents of RPs.

Methodology: Labeling of ¹⁸F, ⁶⁸Ga, ¹⁷⁷Lu, and ^99mTc RPs was performed as per the standard procedures. Cell concentrations of MO (Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Candida albicans) were maintained at 55–65 CFU. Single patient dose in minimum volume was considered for this study (diagnostic: 15–20 mCi and therapeutic: 195–200 mCi). Two methods were adopted to study the viability of MO: in thefirst method, MOs were spread on plates which were prior spread with RPs and dried, and in the second method, RPs along with MO were inoculated in liquid media.

Key Results: Viable CFUa of MO were observed (recovery: 90%–95%) in all of our studied RPs, except [^99mTc] DTPA, [¹⁸F]FLT, and [¹⁸F]FMISO, where recovery was <50%. Luxuriant growths were observed in all the media bottles containing inoculums of studied MO and RPs.

Research Highlights: Emitted radiations from RPs (single patient dose) do not decrease the viable CFU, do not affect the growth rate, and hence will not lead to false negative results in sterility test. Further, it can be concluded that viability of MO in various RPs largely depends on its chemical constituents.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 57:154805 : Can adjuvant radioiodine therapy in carcinoma thyroid patients lead to control/eradication of coexisting Helicobacter pylori infection?

Sunita Sonavane ¹, Priti Fergose ¹, Gaurav Malhotra ¹, B P Tiwari ¹, Ramesh Asopa ¹, Sandip Basu ¹

Rationale: A significant number of thyroid cancer patients harbor coexisting Helicobacter pylori infection, similar to general population. It is not known whether radioiodine concentration in stomach mucosa can irradiate H. pylori leading to its control or eradication. Therefore, the aim of the study was evaluate bystander therapeutic effect of radioactive iodine on H. pylori infection.

Methodology: This was a prospective observational study involving 58 patients of thyroid carcinoma who underwent a baseline 14-C urea breath test (UBT) before 131-I therapy. Based on the results, these were categorized as (a) positive (≥200 dpm) (b) equivocal (>50–199 dpm), and (c) negative (<50 dpm) for H. pylori infection. Positive and equivocal test patients were followed up after 1^st and 3^rd month of 131-I therapy with repeat 14-C UBT. A fall in the counts on UBT was considered as “control” while a negative follow-up UBT implied “eradication” of H. pylori.

Key Results: The results revealed 25 positive, 7 equivocal, and 26 negative for H. pylori infection. Each of the two groups (positive/equivocal and negative) were categorized into Category I, II, III based on the dose of radioiodine received, viz., - 0–60 mCi,60–180 mCi, and 180–250 mCi, respectively. Radioiodine led to control of H. pylori in 19 of 25 (75%) and its eradication in 10 of 25 patients (40%) based on report UBT results at 1 and 3 months. The therapeutic effect was dose dependent, number of responders being twice in high-dose therapy group as compared to low-dose (0–60 mCi) radioiodine therapy.

Research Highlights: Radioiodine therapy has hitherto unknown dose-dependent bactericidal effect on H. pylori infection. In substantial number of cases, radioiodine therapy may cause complete eradication at 1 month of treatment.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 58:124600 : Determination of optimum cutoff value of serum prostate-specific antigen in prediction of skeletal metastases on technetium-99m whole-body bone scan by receiver operating characteristic curve analysis

P Ram Manohar ¹, Tanveer A Rather ¹, Shoukat H Khan ¹

Introduction: Elevated serum prostate-specific antigen (Sr.PSA) levels have high predictive value for skeletal metastases; however, there is no consensus regarding cut-off value of Sr.PSA above which bone scan is indicated. This study was performed to find out the accuracy of Sr. PSA test in prediction of skeletal metastases on bone scan and to find optimum cutoff value of Sr.PSA to exclude the bone scan in staging of prostate cancer.

Materials and Methods: Retrospective analysis of medical records of 305 prostate cancer patients referred to nuclear medicine for bone scan between June 2012 and June 2015 was done. Out of 305 patients, 13 cases were excluded due to nonavailability of Sr.PSA. Technetium-99m methylene diphosphonate bone scan was performed with standard protocol.

Results: Out of 292 cases, 174 patients (59.58%) had positive bone scan for metastases and 118 (40.41%) patients had negative scan for metastases. 44 (15.06%) patients had super scan. On comparison of mean Sr.PSA levels between positive and negative groups, we found significant Sr.PSA levels (P< 0.001). We used receiver operating characteristic (ROC) curve to find out accuracy of Sr.PSA test in prediction of skeletal metastases on bone scan and to know optimum cutoff value of Sr.PSA to avoid the unnecessary bone scans. Area under ROC curve was 0.878 (87%). This indicates the accuracy of Sr.PSA test in prediction of skeletal metastases on bone scan was good. Optimum cutoff value of Sr.PSA to avoid the bone scan in staging of prostate cancer was <29.1 ng/ml with sensitivity and specificity of 89.0% and 74.6%, respectively.

Conclusion: With this study, we conclude accuracy of Sr.PSA test in prediction of skeletal metastases is good. Optimum derived cutoff value of Sr.PSA for positive skeletal metastases is >29 ng/ml and that bone scan may be excluded in patients who have Sr.PSA >29 ng/ml.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 59:130749: ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography in the predicting disease prognosis in chondrosarcoma patients suspected clinical recurrence

Shelvin Kumar Vadi ¹, Arun Kumar Reddy Gorla ¹, Ashwani Sood ¹, Rajender Kumar ¹, Ramesh Sen ¹, Nandita Kakkar ², Bhagwant Rai Mittal ¹

Rationale: The aim of the study is to analyze the diagnostic and prognostic utility of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with recurrent chondrosarcoma. FDG PET/CT uptake and tumor grade were used with an aim to better prognosticate patients using combination of PET/CT finding and tumor grade in thefirst attempt to predict disease-specific survival in the specific clinical setting of recurrence evaluation.

Methodology: Retrospective analysis of FDG PET/CT findings in 31 previously treated patients (46 studies) was done. All patients had a follow-up with mean period of 40.7 ± 23.9 months (range 3–77) from the date offirst PET/CT study. Kaplan–Meier disease-specific survival analysis was made with respect to tumor grade, FDG uptake at the recurrent primary sites, and a combination of grade and FDG uptake as parameters.

Key Results: Recurrence (local and distant) could be shown by FDG PET/CT in 28/46 studies (60.8%) with a sensitivity of 88.9% and specificity of 78.9%. The median maximum standardized uptake value (SUV_max) at the recurrent primary sites differed significantly (P = 0.008) in the three tumor grade groups with increasing median SUV_max in higher grades. There was significant difference in median SUV_max between different tumor grade groups except between grade II and III. Recurrent primary site SUV_max cutoff of 6.15 derived from the receiver operating characteristics curve yielded significant difference (P < 0.001) in mean disease-specific survival time in Kaplan–Meier survival analysis. Significant difference in survival was also noted between three different tumor grade groups (P = 0.016). The combination of SUV_max and grade improved the survival prediction than with grade alone.

Research Highlights: In recurrent chondrosarcoma patients, the recurrent primary site FDG uptake was found to be a reliable prognostic factor with respect to disease-specific survival, in addition to grade. PET/CT in recurrence setting has the potential to predict tumor grade and survival and may assist in clinical management in this patient group.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 60:061918 : Assessment of response to initial radio-active iodine treatment in operated cases of differentiated thyroid carcinoma at 1-year follow-up using the dynamic risk assessment criteria of ATA 2015 in a tertiary care center

Sayak Choudhury ¹, Archi Agrwal ¹, Gouri Pantvaidya ¹, R V Asopa ¹, Sneha Shah ¹, Nilendu Purandare ¹, Ameya Puranik ¹, V Rangarajan ¹

Rationale: The 2015 ATA guideline suggests a radically different approach for follow-up of differentiated thyroid carcinoma (DTC) patients using biochemical parameters and imaging techniques and also suggests further modification of the risk stratification according to the follow-up data. The current study uses the dynamic risk assessment criteria proposed by ATA to evaluate the various responses to radio-active iodine (RAI) usage in DTC, in a clinical setting.

Methodology: A total of 134 patients with DTC posttotal thyroidectomy and post-RAI treatment in the years 2014–2015 with follow-up of at least 1 year were retrospectively reviewed, following approval from institutional ethics committee. Patients were categorized using dynamic risk stratification criteria of ATA 2015 using the follow-up data.

Key Results: Among the 134 patients, number of low-, intermediate-, and high-risk patients was 26, 65, and 43, respectively, during initial risk assessment. At 1-year follow-up, 91 had excellent response, 24 indeterminate response, and 18 structural incomplete response and single patient had biochemical incomplete response. 75% of the intermediate-risk, 88.5% of the low-risk, and 48.8% of the high-risk patients showed excellent response. 3.07% of the intermediate-risk patients showed persistent structural disease. Among the patients with structural incomplete response, 13 had distant metastasis and 5 had nodal recurrence.

Research Highlights: Majority of the low- and intermediate-risk patients show excellent response at 1-year follow-up. All the patients with distant metastases and 3.07% intermediate-risk patients showed persistent structural disease at follow-up and required retreatment.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 61:183611 : Luminescent lanthanides as targeted theranostic and cellular imaging agents

Ashis K Patra ¹, Khushbu Singh ¹, Swati Singh ¹, Sri Sivakumar ¹

Rationale: Luminescent lanthanide complexes have multiple unique advantages in bioimaging and live-tracking of therapeutic loads and theranostic applications due to unrivalled optical features. They possess originating from shielded 4f-electrons by outer 5s 25p 6 subshells. Lanthanide probes with long luminescence lifetime, bright luminescence, high quantum yield, remarkable photostability, and large ligand induced-Stoke’ shifts are highly desirable for in-situ interference-free biological imaging by time-gated fluorescence microscopy.

Methodology: Development of photostable nucleoli stains remains vital in understanding complex nucleolar compartments and process of building ribosomes. Here, we report water-soluble luminescent heterometallic Ln-Pt2 bioprobes as “lanthanoplatins”: [{cis-Pt(NH3)2(Cl)}Ln(L)(H2O)](NO3)2 (Ln = Eu [1, europlatin] and Tb [2, terbiplatin]), containing two cisplatin moieties as DNA cross-linkers for targeting nuclear DNA showing strong luminescence from f-f emission of LnIII and localizing at nucleoli of cancer cells for drug delivery and nucleoli staining.

Key Results: In this systematic study, two highly luminescent water-soluble heterometallic LnPt2 probes (1, 2) show efficient nucleoli staining abilities through formation of Pt-DNA crosslinking in nuclei. Significant cellular uptake via macropinocytosis and distinctive nucleoli localization through intrinsic emission from EuIII or TbIII observed through confocal fluorescence microscopy along with their remarkable photostability.

Research Highlights: This study represents a set of significant and novel findings in the area of application of luminescent lanthanide complexes in organelle-specific bioimaging. This underscores the opportunities available toward designing lanthanide-based low molecular weight nucleolus stains with multimodal imaging ability and having excellent potential to visualize detailed substructures of nucleolar compartments and nucleolar changes in malignant cells.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 62:172453 : Radiolabeling and biological evaluation of ⁶⁸Ga-NOTA-ubiquicidin fragment for prospective infection imaging

Archana Mukherjee ^1,², Jyotsna Bhatt ^1,², Aruna Korde ^1,^2,³, Haladhar Dev Sarma ⁴, Krishnamohan Repaka ³, Ashutosh Dash ^1,²

Rationale: To develop positron emission tomography (PET) agent for infection imaging using ubiquicidin (UBI) peptide fragment labeled with ⁶⁸Ga.

Methodology: In this study, peptide 31-38 fragment of UBI conjugated with macrocyclic chelator NOTA was synthesized. Radiolabeling of NOTA-UBI (31-38) with ⁶⁸Ga was optimized and quality control analysis was done by chromatography techniques. In vitro evaluation of ⁶⁸Ga-NOTA-UBI (31-38) complex was carried out in Staphylococcus aureus. Biodistribution studies of ⁶⁸Ga-NOTA-UBI (31-38) in normal animals and in animal model of infection were also carried out.

Key Results: ⁶⁸Ga-NOTA-UBI (31-38) could be prepared in high radiochemical yields with high radiochemical purity using peptide conjugate in sodium acetate. The complexes showed retention time of 16.2 min in standardized high pressure liquid chromatography radiochromatogram. Statistically significant inhibition in uptake of ⁶⁸Ga-NOTA-UBI (31-38) was observed with 100 fold excess of cold UBI (29-41) indicating specificity of the agent for bacteria. Significant uptake of ⁶⁸Ga-NOTA-UBI (31-38) in infected muscle was observed compared to inflamed and normal muscle. No significant uptake in vital organs and clearance by renal route was observed at 1 h p.i for the complex.

Research Highlights: This is thefirst report on ⁶⁸Ga labeling of NOTA-UBI (31-38) fragment and its biological evaluation for prospective infection imaging

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 63:000631 : Correlation of Serum PSA with 99mTc MDP Bone Scan in Newly Diagnosed Patient of Prostate Carcinoma: Should we Follow Western Guidelines?

Amit Sharma ¹

Objective: The necessity of bone scans in newly diagnosed prostate cancer patients is still a matter of debate. We attempt to evaluate the validity of currently published guidelines by analyzing bone scan results in newly diagnosed prostate cancer (PCa) patients to determine the optimal staging strategies.

Materials and Methods: Between January 2011 and July 2014, there were 362 consecutive newly diagnosed PCa patients at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Bone scans were performed for all patients at initial staging. Patients positive for bone metastasis were characterized at diagnosis in terms of age, prostate-specific antigen (PSA) level, Gleason's score (GS), and clinical stage. We analyzed the sensitivity and specificity of the American Urological Association (AUA) best practice policy, European Association of Urology guidelines, National Comprehensive Cancer Network guidelines, and the classification and regression tree by Briganti et al. for diagnostic performance in predicting bone metastasis.

Results: A total 73 of 362 (20.2%) patients were diagnosed with bone metastasis. Patients positive for metastasis on bone scans had significantly higher PSA levels (median: 196.5 ng/mL, interquartile range: 904.3 vs. median: 18.5 ng/mL, interquartile range: 35.7; P< 0.001) and higher GSs (8.5 ± 1.0 vs. 7.0 ± 1.6; P< 0.001) than those with negative bone scan results. Pairwise comparisons in receiver operating curve analysis demonstrated that the AUA guidelines had a larger area under the curve than the other guidelines.

Conclusion: The current AUA guidelines for the recommendation of staging bone scans had better prediction and application rates than other guidelines in our patient cohort.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Medical Physics: OP 64:133226 : Biokinetic studies of ¹⁷⁷Lu-DOTATATE in patients with advanced/metastatic neuroendocrine tumor receiving peptide receptor radionuclide therapy

Kamal Deep ^1,², Gaurav Wanage ³, Sudip Sahoo ³, Pravind Maletha ⁴, Aadhil Adnan ⁴, Sandip Basu ^2,⁴, Tapas Das ^3,⁴, Sharmila Banerjee ^2,⁴

Rationale: The primary aim of this study was to determine the effective half-life and percentage of radioactivity that follows particular half-life trend in patients undergoing peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE.

Methodology: Thirty patients (23 males and 7 females), with positive somatostatin receptor over-expression in neuroendocrine tumor (NET), who underwent PRRT with ¹⁷⁷Lu-DOTATATE were enrolled in this study. All patients underwent whole-body γ-scintigraphy (anterior and posterior planar acquisitions) at 0.5 (prevoid) and 2, 12, 24, and 72/96 h (postvoid) after intravenous administration of therapeutic dose of ¹⁷⁷Lu-DOTATATE (5.03–8.40 GBq). From the series of γ-scintigraphy images, the following were obtained: effective half-lives, radioactive decay kinetics, and fraction of radioactivity that follows particular half-life trend.

Key Results: ¹⁷⁷Lu-DOTATATE clearance inside the patient's body followed bi-exponential decay (two components) in 25 patients, whereas in 5 patients, it followed mono-exponential decay. The effective half-life of thefirst component ranged from 0.82 to 4.90 h with mean ± standard deviation (SD) of 2.23 ± 0.95 h and the effective half-life of the second component was 12.15–71.94 h with mean ± SD of 36.20 ± 16.47 h. The fraction of radioactivity that followed thefirst component was 0.51 ± 0.17 (range, 0.21–0.76) while 0.49 ± 0.17 (range, 0.24–0.79) fraction of administered radioactivity followed the second component. The mean effective T_1/2 in case of mono-exponential decay was estimated to be 12.58 h.

Research Highlights: In this study, individual biokinetic study was carried out in patients of metastatic/advanced NETs, undergoing therapy with ¹⁷⁷Lu-DOTATATE. It was found that ¹⁷⁷Lu-DOTATATE follows bi-exponential decay kinetics inside patient's body. Thefirst component is due to radioactivity in blood circulation and the second component is due to uptake of radioactivity in somatostatin receptor-positive tumor/organs and metastatic sites. Greater the uptake and longer the effective half-life of the radiopharmaceutical in the tumor, higher will be the absorbed dose to the tumor which would result in higher therapeutic efficacy.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 65:413356 : Linear electron accelerator-based radioisotope generation

Abhay Deshpande ¹, Tanuja Dixit ¹, R Krishnan ¹, Anil Kumar Mishra ¹, Sanjay Pethe ¹, Shubhra Chaturvedi ¹, Puja Panwar ¹, Sandesh Bhat ¹, Ganesh Gaikwad ¹, Paresh Jadhav ¹, Manoj Kumbhare ¹, C S Nainwad ¹, Sandeep Name ¹, R Sandeep Kumar ¹, Sameer Kiran Thakur ¹, Mandar Vidwans ¹, Mathe ¹, Krutika Natu ¹

Rationale: Technetium99m is one of the most widely used radioisotopes in the diagnostics procedures worldwide. In 2015, SAMEER initiated development of high-energy, high-beam power electron linac for generation of⁹⁹ Mo from which ^99mTc will be eluted.

Methods: In this project, SAMEER has focused on development of high current linac technology while INMAS is working to establish the elution process of ^99mTc from⁹⁹ Mo. We are working to establish 30 MeV electron accelerator which will generate beam power of around 8–10 KW. The base design is based on side-coupled, standing-wave accelerator technology established by SAMEER for radiotherapy linac in India. Two-stage acceleration will help achieve desired beam energy and power. Solid=state modulator will be used to generate necessary radiofrequency power to drive the linac. FPGA-based computerized control system developed at SAMEER will be used to control the accelerator as well as all other subsystems.

Results: In this paper, we list the design details of linac and subsystems designed at SAMEER. We also compare some technologies with cyclotron-based system.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 66:412563 : Target design and activity estimation from a 30 MeV electron accelerator for radioisotope generation

Tanuja Dixit ¹, Aqsa Shaikh ¹, S V Suryanarayana ¹, Abhay Deshpande ¹, R Krishnan ¹, R Thomas ¹

SAMEER is developing a high energy and high-beam power electron linear accelerator for radio-isotope generation.^[1] Technetium-99m is a very important radio-isotope in nuclear imaging. It is eluted from Mo-99 which has a half-life of 66 h. Two approaches for Mo-100 to Mo-99 conversion were studied. In converter target approach, high energy electronsfirst fall on high Z target to produce bremsstrahlung radiation via (e, γ) reaction. These photons then bombard the enriched Mo-100 target to produce Mo-99 via (γ, n) reaction. In the second approach, direct irradiation of Mo-100 target with electrons is studied using GEANT4 simulations. The comparison of the activity in both the methods is done. Furthermore, a large flux of neutrons is produced during the reaction. These neutrons can be used to irradiate natural Mo, thus enhancing the activity.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 67:114536 : Image-based dosimetry for patients undergoing 188Re-Lipiodol trans-arterial radioembolization

Jephy Joseph ¹, R Yurekha ¹, Pedro L Esquinas ^1,², Anna Celler ^1,², E R Radhakrishnan ¹, Indira V Upadhya ¹, K K Kamaleshwaran ¹, Ajit S Shinto ¹

Aim: The purpose of this study was to determine the in-vivo pharmacokinetics and patient specific dosimetry for patients undergoing Re188-HDD lipiodol Transarterial radioembolization (TARE) based on quantitative posttreatment images.

Introduction: Scintigraphic images have been a valuable source of information for dosimetric studies and quantifying the localized dose more accurately and monitoring of radiation risk for nontarget organs in any radionuclide therapeutic procedures. In the present study, we have performed personalized dosimetry of 13 patients with HCC undergoing ¹⁸⁸Re-AHDD-lipiodol TARE using posttreatment images for quantification.

Methods: Imaging protocol was set as a whole-body scan (anterior, posterior) along with single photon emission computed tomography-computed tomography of liver at 3, 24, and 48 h. The bio-distribution, pharmacokinetics, and normalized doses per injected activity were estimated for the following regions of interest: tumor, liver, lungs, stomach, kidneys, and spleen (were performed using QDOSE, a software for dosimetry calculations in radionuclide therapies from ABX-CRO, Germany).

Observation: The average effective half-life in tumor was found to be ~12.5 ± 2.0 h (range 9.8-16 h). Average normalized doses per injected activity in tumor, liver, and lungs were found as 23.5 ± 40.8 mGy/MBq (range 2.32–162 mGy/MBq), 2.12 ± 1.78 mGy/MBq (range 0.48–7.8 mGy/MBq) and 0.27 ± 0.13 mGy/MBq (range 0.11–0.54), respectively. Dose received by tumor is 5–10 times the dose received by liver.

Conclusion: The large inter-patient variations of these normalized doses strongly indicate the significance of performing patient-specific dose calculations. It was found that the radiation burden received by the adjacent nontarget regions were within acceptable limits, normal liver received maximum of ~13 Gy (acceptable limit < 30 Gy) and lungs maximum of 0.9 Gy (acceptable limit <12 Gy) according to Zanzonico et al. 2004 protocol. Imaging at 3 h and 24 h were sufficient for the accurate dosimetry.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 68:133714 : Measurement of radiation exposure to radiation professionals during positron emission tomography/computed tomography-guided biopsy

Tamanna Lakhanpal ¹, Ankit Watts ¹, Nivedita Rana ¹, Rajender Basher ¹, Harmandeep Singh ¹, Bhagwant Rai Mittal ¹

Introduction: Molecular imaging provides information at cellular and molecular levels. Currently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is the widely used imaging modality for the diagnosis of various cancers. However, imaging alone cannot verify the cancerous condition. Biopsy remains the most definitive diagnostic procedure in the diagnosis of the condition and in its further management. The current aim of the study is to estimate the radiation exposure to the radiation professionals during PET/CT-guided biopsy.

Materials and Methods: This prospective study was conducted at PGIMER during the period from August 2016 to May 2017. This study included 50 patients who were referred for PET/CT-guided biopsy (18 lung, 10 bone, and 22 miscellaneous lesions). Out of which, there were 36 males and 14 females with a mean age 54 ± 15 years (17–78 years). All the patients were administered a dose of 3–6 mCi of ¹⁸F-FDG depending upon the period of biopsy. All the professionals involved in biopsy procedure were given a calibrated pocket dosimeter. The radiation exposure measurements were made at 1 m distance and at the body surface using a gun monitor. Mean and standard deviation values were calculated for exposure and exposure rate measurements, time elapsed, and time taken for biopsy.

Results: It was observed that the exposure rate was reduced at 1 m compared to surface exposure rate by a factor of 10.7. Furthermore, the exposure rate in bone biopsies was less when compared to lung biopsies, attributed to the administered activity, and time lapsed between the injection and time of biopsy. It was also found that personnel performing received higher exposure than the personnel assisting in all groups. Using average personnel exposure in all groups, the estimated exposure in a year comes out to be 0.9 mSv/year.

Conclusion: The radiation exposure to the personnel performing PET/CT-guided biopsy is within limits specified by the regulatory authorities. The PET/CT-guided biopsy was found to be a safe interventional procedure.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 69:085834 : Acceptance, reference, and routine tests for single and multiple head single photon emission computed tomography systems

Dibya Prakash ¹

Rationale: Quality assurance is a crucial part of all aspects of nuclear medicine practice. Three types of quality tests such as acceptance, reference, and routine tests are carried out for obtaining optimum image quality and quantitative data in single photon emission computed tomography (SPECT) and planar imaging. The acceptance of an instrument following its receipt and installation is a critical step toward the achievement of high-quality performance. At the time of acceptance testing, reference tests should be carried out and be compared during routine testing. Tomographic system is much more sensitive to poor performance with respect to the parameters measured in conventional planar imaging. Therefore, additional parameters are required to be carried out for optimum tomographic performance: (1) tomographic uniformity, (2) tomographic resolution, (3) linearity of tomographic response, (4) quantitative accuracy in tomography, (5) precision of estimation of the center of rotation, (6) tomographic sensitivity – slice and volume, (7) tomographic signal-to-noise ratio, (8) tomographic contrast, and (9) slice thickness. There are some additional components of the system, which are interfaced with imaging system, also to be monitored such as patient bed (pallet or couch), gantry, rotation, controller, emergency stop and other patient safety devices, and position readout devices for best results.

Methodology:

(1)
Tomographic uniformity: Tomographic uniformity is the uniformity of the reconstruction of a slice through a uniform distribution of activity and performed with ECT (Jaszezak) phantom using 360° of angle of rotation, 800 K counts per projection on 128 × 128 matrix and 120 projections
(2)
Tomographic resolution: Tomographic resolution is defined in terms of the FWHM of the filtered back-projection reconstruction of a point source in a transaxial slice. It is measured on the reconstructed image. Tomographic resolution determines the sharpness of the image
(3)
Linearity of tomographic response: Linearity activity response of a SPECT system can be constructed with a collection of tubes, each with a specific, known activity concentration, in an array of positions inside a circular cylinder of 20 cm diameter or a torso-shaped cylinder filled with a uniform solution of water. The linearity of the system is estimated from plot obtained
(4)
Quanitative accuracy in tomography: The quantitative accuracy of the system is described by the deviation from the true value involved in estimating the activity concentration at some position in the reconstructed image in absolute terms, i.e., Becquerels per milliliter. The value estimated by the system is compared with the actual value at some point within the object
(5)
Precision of the estimation of the axis of rotation: The perpendicular line passing through the axis of rotation is supposed to pass through the center (the central axis) of the projection image. The difference of distance is termed the center of rotation offset. It can be estimated as a function of the angle of rotation and is critical in setting up a tomographic system
(6)
Tomographic sensitivity – slice and volume: The tomographic sensitivity is estimated in terms of number of counts detected for known activity in a standard phantom similar to planar sensitivity. A known activity concentration is placed into a specified phantom. The number of counts detected is then determined for a slice through the object and for the complete object. The result is expressed as counts detected per se cond per unit of activity concentration
(7)
Tomographic signal-to-noise ratio: It depends on a number of parameters such as counts acquired, distribution of the counts, reconstruction process and other components of the reconstruction algorithm such as scatter and attenuation correction. It is determined by number of counts in a pixel (or for the whole field of view) according to Poisson statistics and variance equal to the number of counts in that pixel
(8)
Tomographic contrast: Tomographic contrast determines the detectability of small lesions. Tomographic contrast decreases as the size of the object becomes smaller. It is determined by placing a sphere of known size filled with activity. This is compared with background activity to know the value of contrast
(9)
Slice thickness: Slice thickness describes the spatial resolution of the system along the Z axis for that reconstruction. FWHM, measured from the response of the system to a point source placed at known radial distance from the axis of rotation, along a line parallel to the axis of rotation determines the slice thickness and is not constant with respect to position within the transaxial slice. Important values are the slice thickness at the center and 10 cm from the axis of rotation.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 70:202628 : Role of two-dimensional Gaussian filter in image noise removal

Chandan Singh Bisht ¹, Anil Kumar Pandey ¹, Akshima Sharma ¹, Chetan Patel ¹, C S Bal ¹, Rakesh Kumar ¹

Rationale: Size of filter plays important role in image noise removal. The present study investigates the effect of filter size on image noise removal.

Methodology: A digital phantom with image matrix size 128 × 128 was created. It consists of eight objects (three squares, one circle, three solitary rectangular bars, and one triangle made up of six rectangular bars, mimicking hot spots) of different sizes. Gaussian noise with variance ranging from 0.003 to 0.15 incremented at the rate 0.003 was added to the phantom image, thus creating 50 noisy images. Gaussian filters of 3, 5, 7, 9, and 11 pixel size were applied to noisy images. The output image quality was assessed both subjectively and objectively using peak signal-to-noise ratio (PSNR).

Key Results: At minimum noise level, for filter sizes 3 and 11 pixels, the PSNR value of output image was 20 dB and 15 dB, respectively, while at maximum noise level, it was 15 and 14 dB. Visually, at maximum noise level, better image quality, i.e., sharp image with very minimum edge distortion was noticed with 3-pixel size filter; however, amount of noise removal was least in comparison to 5, 7, 9 and 11 pixel size filter. The maximum noise removal, maximum edge distortion, and elimination of objects of size less than the filter size was found with 11-pixel size filter.

Research Highlights: Better image quality was noticed with 3-pixel size Gaussian filter.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 71:410962 : Analysis of effect of sample volume and dead time on activity measurements in a gamma-ray spectrometer for radioisotope¹³¹ I

Vasumathi ¹, K Rajesh ¹, P S Maya ¹

Introduction: The drainage system of the high-dose¹³¹ I therapy isolation ward is connected to a delay tank for the radioactive waste to decay till the activity concentration is <0.6 μCi/l (as per AERB regulation) before discharge into the general sewage system. Gamma-ray spectrometer is a radiation measuring equipment which is employed to measure gamma emitting radioactive samples of small quantity. Sample volume and dead time have significant effect on the counting rate while counting in gamma-ray well counters. Usually, the volume of sample collected from delay tank for measurement is more than the required volume to be used in well counters. The count rate of a defined activity in a gamma counter decreases consistently with serial dilution and vice versa. However, this proportionality in count rate is lost as the volume approaches and exceeds the top of detector well. Considering this phenomenon, we aimed to analyze the effect of sample volume and dead time on activity measurements in a gamma-ray spectrometer for radioisotope¹³¹ I and further establish the upper limit of activity and volume of¹³¹ I samples for accurate measurement.

Materials and Methods: (1) The dead time was calculated for the various radioactive samples ranging from 0.5 μCi to 10 μCi. The observed count of each activity was corrected for dead time to derive true count. The derived true counts were further analyzed. (2) A small sample of radioactive solution of¹³¹ I activity ranging from 0.5 μCi to 6 μCi was measured in a calibrated gamma-ray spectrometer which was further diluted progressively with normal saline up to 6 ml and the counts were recorded.

Result: (1) Least variation in dead time was observed for the activity measurement ranging from 0.5 μCi to 8 μCi and a drastic increment in dead time was observed beyond 8 μCi. (2) Least variation in counts was observed for an activity measurement in volumes ranging from 0.1 ml to 3ml and a drastic variation was observed when the volume was more than 3 ml.

Conclusion:¹³¹ I activity of up to 8 μCi in a volume of up to 3 ml can be accurately measured in a gamma-ray spectrometer.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

Women in Nuclear Medicine and Miscellaneous: OP 72:166101 : Exploitation of solid targetry for scandium-44 production at INMAS: A potential alternative to generator-produced radioisotopes

Shubhra Chaturvedi ¹, Puja Panwar Hazari ¹, Anil K Mishra ¹

Objective: The aim of this work is to develop an alternative method of production of long-lived positron emission tomography (PET) radioisotopes (44-scandium) in quantities and quality useful for medical purposes in India. 44Sc is useful in PET imaging (T_1/2= 3.97 h; E_β+= 1475 keV, 94.3%). The longer half-life permit longer radiolabeling manipulations and transportation to remote areas. It can be a potential alternative to 68Ga in clinical PET diagnosis, offering longer half-life and better resolution than 68Ga. Production options for 44Sc include 44Ti/44Sc generator or cyclotron production. At INMAS, the production was planned using 16.5 MeV medium-sized medical cyclotron at INMAS. The produced 44Sc was planned to label the well-characterized DOTA analogs. The tracers will be assessed with respect to their in vivo pharmacokinetic imaging capacity, as well as the total radiation dose to the patients in a head-to-head comparison with ⁶⁸Ga-labeled analogs.

Materials and Methods: The entire production was planned as stepwise optimization with following steps involved: (a) development of a targetry system (b) development/optimization of the separation method, and (c) chelator development for scandium. The production of 44Sc from natural 40-calcium was planned using the 16.5 MeV medium-sized medical cyclotron at INMAS. Pellets of target were prepared by pressing method and placed in aluminum target. The target was cooled using water and air combination and irradiated for varying time (5-10 min) and varying beam currents (5–10 μA). The absolute radioactivity of 44Sc and other obtained radionuclides was measured by.

Results and Discussion: A prototype shuttle was designed which could result in a homogenous target and ensure that there will be higher⁴⁴ Sc yields. Calculations were carried using the beam energy to arrive at the thickness of the shuttle. By beam optimization experiments, it was inferred that 10 μA beam current with an irradiation time of 10min was sufficient to have radioactivity. To optimally separate 44Sc from the irradiated calcium targets, a separation system was designed. Briefly, the irradiated natCaCO3 target was dissolved in acid solution and passed through a combination of Dowex and DGA column to separate scandium.

Conclusion: The present study attempts to establish the use of nucleolipids as imaging agent for brain. Feasible synthesis of DAU-loaded Ag nanoparticles has been synthesized along with its characterization.

Indian J Nucl Med. 2017 Dec;32(Suppl 1):S2–S32.

OP 73:180930 : Multiple biological activities and docking studies of metronidazole triazole hybrids

Beena Negi ¹

Rationale: Metronidazole has been used for the treatment of bacterial and protozoal infections. However, this drug has developed resistance to some strains of bacteria and protozoa. We anticipated that hybrid molecule that contains metronidazole and triazole, one of the most active and widely studied pharmacophore, will lead to a molecule of biomedical importance. For this, we decided to functionalize hydroxyl functionality of metronidazole (MTZ) in such a way that MTZ can be covalently linked to triazoles. Staphylococcus aureus is the leading cause of infections in the hospitals worldwide and it has developed resistance against methicillin (methicillin-resistant S. aureus [MRSA]). Among the protozoal infections, amoebiasis is the third leading cause of death caused by Entamoeba histolytica. Our study focuses on synthesis as well as the antibacterial and antiamoebic activity of the MTZ-triazole hybrids.

Methodology: A series of MTZ-triazole hybrids were synthesized with different substitution pattern on the triazole ring. These compounds were docked against penicillin-binding protein 2a(PBP2a) crystal structure from MRSA and E. histolytica thioredoxin reductase (EhTrR), which is a promising target for the treatment of amoebiasis. Key

Results: The MTZ-triazoles demonstrated potent antibacterial activity against Gram-positive and Gram-negative bacteria (IC₅₀0.003–0.350 μg/mL).^[2] These MTZ-triazoles were also found to be active against MRSA. One of the compounds was found to be effective at 4 μg/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced up to 1 μg/mL when this compound was used in combination with oxacillin in 1:1 ratio. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies showed that these compounds interact with Thr600, Ser598, Asn464, His583, and Tyr446 in the active site of PBP2a crystal structure from MRSA^[3] MTZ–triazole hybrids and metronidazole-triazole-styryl hybrids exhibit activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole with an IC₅₀ value of 8.4 nM, was significantly more active than the standard drug MTZ. Docking studies with EhTrR revealed that this compound may act as an EhTrR inhibitor.^[4] Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR. All the compounds were found to be nontoxic in THP-1 cell line up to a concentration of 50 μM.

Research Highlights: (i) Synthesis of MTZ-triazole and MTZ-triazolestyryl hybrids, (ii) Potent antibacterial and antiamoebic activity of the hybrids (iii) Docking against PBP2a for MRSA and EhTrR for amoebiasis

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A S Rahul

Shwetal Pawar

Mangala Ghorpade

Suruchi Shetye

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Ankur Pruthi

Promila Pankaj

Ritu Verma

Ethel S Belho

Harsh Mahajan

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Ashwani Sood

Priya Bhusari

Jaya Shukla

Bhagwant Rai Mittal

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Akshima Sharma

Anil Kumar Pandey

Anant Mohan

Ashu Seith Bhalla

V Sreenivas

Mehar Chand Sharma

Chandan J Das

Sanjay Thulkar

Chetan D Patel

C S Bal

Anshul Sharma

Rakesh Kumar

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Virendra Singh

Anish Bhattacharya

Baljinder Singh

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Rakesh Joshi

R Vishnukumar

H Dhanapathi

Nandin Pandit

Madhusudhanan Ponnusamy

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M S Bharadwaj

P A Meivel

P Madhusudhanan

H Dhanapathi

Nandini Pandit

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A Sreekumar

Lekha M Nair

V M Pradeep

OP 9:165050 : Radioiodine therapy in a thyroid cancer patient with chronic renal failure on hemodialysis: Therapeutic challenges and radiation safety issues

Pravind Maletha

Kamaldeep

Gaurav Malhotra

Digish Shah

Rohit Ranade

Sushma Kaisar

ShriramTervankar

Ashok Kriplani

Ramesh Asopa

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L Peethamber

Nandini Pandit

H Dhanapathi

P Madhusudhanan

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Rohit Kakde

Ameya Puranik

Archi Agrawal

Sneha Shah

Nilendu Purandare

V Rangarajan

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Pankaj Dheer

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Yeseshvi Kilambi

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