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Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades it is known that cholecystokinine-2 receptor (CCK2R) is a promising target for the treatment of MTC with radiolabeled minigastrin analogues. Unfortunately, kidney toxicity precluded their therapeutic application so far. In 6 consecutive patients we evaluated with advanced 3D dosimetry whether improved minigastrin analogue 177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received two injections of about 1 GBq (~80 µg) 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random cross-over sequence in order to evaluate biodistribution, pharmacokinetics as well as tumor- and organ dosimetry. ECG, blood count and blood chemistry were measured up to 12 weeks after administration of 177Lu-PP-F11N to assess safety. Results: In all patients 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach and kidneys. Altogether 13 tumors were eligible for dosimetry. The median (interquartile range = IQR) absorbed dose for tumors, stomach, kidneys and bone marrow was 0.88 Gy/GBq (0.85-1.04), 0.42 (0.25-1.01), 0.11 (0.07-0.13) and 0.028 (0.026-0.034). These resulted in a median (IQR) tumor-to-kidney dose ratio of 11.6 (8.11-14.4) without SG and 13.0 (10.2-18.6) with SG, which were not significantly different (P = 1.0). The median (IQR) tumor-to-stomach dose ratio was 3.34 (1.14-4.7). Adverse reactions (mainly hypotension, flushing and hypokalemia) were self-limiting and not higher than grade 1. Conclusion:177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With little kidney and bone marrow radiation dose 177Lu-PP-F11N shows promising biodistribution. The dose limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N.

393 Objectives: The currently available PET tracers i.e. 18F-FET and 11C-methionine have proven high diagnostic efficacy in GBM. However, the development of SPECT based tracers is always viewed as a cost-effective alternate to PET imaging. The aim of the present study was to determine the diagnostic efficacy of 99mTc-labelled MDM (bis-methionine) SPECT in the diagnostic work up in glioma. Methods: The present study was conducted in 143 glioma patients (101M: 42F; mean age 41.97±11.9 years; range 18-71 years) who were newly diagnosed or previously treated or who were recruited for post-surgical radiotherapy/chemotherapy treatment from December 2014 to August 2018. Amongst, 143 patients, 29/143 (20.0%) were freshly diagnosed patients of glioma and the remaining 114/143 (80.0%) patients were on post-surgery follow-up (radiological/clinical) with chemotherapy/radiotherapy interventions. The patients were subjected to a detailed histopathological tumor analysis (including Ki-67 index), 99mTc-MDM-SPECT, conventional MRI, DSCE-MRI and MR spectroscopy for the disease evaluation at presentation and during the course of follow-up after surgery/chemo/radiotherapy. A total of 227 brain scans (99mTc-MDM-SPECT) and an equal number of conventional MRI scans were performed in 143 patients. The results of the two imaging modalities were compared and correlated with the clinical findings. In a sub-set of patients (n=43), a quantitative DSCE-MRI and MR spectroscopy analysis was done. The results of the later were compared with the 99mTc-MDM-SPECT quantitative results for validation of this technique for accuracy in the glioma detection and characterization. Results: On histopathological analysis, 26/29 patients (pre-surgery group) were diagnosed to have glioma ( G IV-13; G III-04; G II-09) and the remaining 3/29 patients were found to be meningioma. The mean target to non-target (T/NT) ratios of 99mTc-MDM in glioma grade II, grade III, and grade IV patients were estimated to be 2.46±2.3, 7.13±2.2 and 5.16±1.2 respectively. This ratio was much higher (15.9 ±6.8) in meningioma. The ROC curve analysis derived cut-off value of T/NT ratio of greater than 3.08 when used to discriminate low grade from high grade glioma provided 100% sensitivity, 87.5% specificity. In the post-surgery group, the final diagnosis could be made in 72/114 patients. Out of these, 47/72 showed tumor recurrent (Fig.1) or residual disease and the remaining 25 patients showed necrosis. The ROC curve analysis derived cut-off value of T/NT ratio of greater than 1.90 used to discriminate tumor recurrence from necrosis offered sensitivity and specificity of 97.9 % and 92.0% respectively. A similar analysis on DSCE-MRI quantitative data with derived nCBV cut of value of greater than 3.32 for discriminating tumor recurrence versus necrosis provided sensitivity and specificity of 84.6% and 93.0% respectively. MR spectroscopy data analysis estimated the cut-of ratios; sensitivity/specificity of different metabolites i.e. Cho/NAA, Cho/Cr, Cr/NAA, Cr/Cho and Cho/LL to be >1.57, 81.0%/73.0%; >1.64, 85.3%/73.7%; >1.06. 57.1%/ 63.6%; ≤ 0.60, 72.3%/81.0% and >0.90, 71.4%, /50% respectively. T/NT ratio showed a strongest linear correlation with nCBV(r = 0.775, P

111In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]exendin-4 (68Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. Methods:68Ga-DOTA-exendin-4 PET/CT and 111In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. Results: In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive 68Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. 68Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas 111In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. Conclusion: These preliminary data suggest that the use of 68Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.