A head-to-head comparison study of ⁶⁸Ga-DOTA-Exendin-4 and ⁶⁸Ga-DOTA-NOC PET/CT in insulinomas.

Objectives: Comparison of ⁶⁸Ga-DOTA-Exendin-4 and ⁶⁸Ga-DOTA-NOC PET/CT in biopsy proven cases of sporadic benign, malignant and multiple endocrine neoplasia- 1 (MEN-1) associated insulinomas.

Methods: Biochemically proven hyperinsulinemic hypoglycemia patients underwent both ⁶⁸Ga-DOTA-Exendin-4 and ⁶⁸Ga-DOTA-NOC PET/CT in a random fashion within one week. PET/CT images were acquired after intravenous administration of 2-5 mCi of each radiotracer, and images were acquired at 45-60 minutes. Definition: Focal uptake more than the rest of pancreas was considered positive. Maximum standardised uptake value (SUVmax) and SUVmax ratios of lesion/aorta were calculated.

Results: Total 36 patients (median age- 42 years: range= 19-88), females 19) were recruited. Curative surgery in 23 and biopsy only in 2 patients were performed. Remaining 11 patients with no histopathological confirmation, 4 patients were diagnosed to have Insulin autoimmune syndrome, and both scans were negative (true negatives), in 6 patients final diagnosis was not achieved, in which both PET/CTs were negative and 1 patient had focal lesion in both PET/CT scans in tail of pancreas but refused to undergo surgery/biopsy. Twenty five patients with final histopathological confirmation: malignant Insulinoma in 3, adult onset nesidioblastosis in 1, MEN-1 associated insulinoma in 4, and benign sporadic Insulinoma in 17 were reported. The median value of lowest recorded blood sugar among the 25 patients was 36mg/dl (range 23-42). Median serum insulin level was 37.9uU/ml (IQR 24.2-50.7) and median C-peptide was 5.7ng/ml (IQR 3.8-8.0). Multifocal insulinoma was present in one sporadic and one MEN-1 patients (2 lesions in each) thus a total of 23 benign insulinomas. On lesion-based analysis 68Ga-DOTA-Exendin-4 PET/CT was positive in all benign and 2/3 of malignant insulinomas. 68Ga-DOTA-NOC PET/CT was positive in 15 (65%) of benign and all 3 malignant insulinomas. ⁶⁸Ga-DOTA-Exendin-4 PET/CT detected significantly more lesions (25/26= 96%) compared to ⁶⁸Ga-DOTA-NOC PET/CT (18/26=69%; p= 0.02). One patient with adult onset nesidioblastosis had diffuse uptake in the tail of pancreas on ⁶⁸Ga-DOTA-Exendin PET/CT but was negative on ⁶⁸Ga-DOTA-NOC scan. Among 4 patients with MEN-1 multiple pancreatic lesions were present in 3 patients and solitary lesion in one. ⁶⁸Ga-DOTANOC PET/CT showed uptake both in insulinomas (4 lesions) and in non insulinoma NETs, however, as expected ⁶⁸Ga-DOTA-Exendin scan showed uptake only in insulinomas that aided in pancreatic conservation surgery. No significant difference in lesion SUVmax values and lesion to aorta SUVmax ratios were observed between benign and malignant insulinoma lesions on both PET/CTs. No correlation was found between Ki67 index and SUV values of both PET/CTs.

Conclusions: ⁶⁸Ga-DOTA-Exendin-4 PET/CT has better lesion localization compared to 68Ga-DOTANOC PET/CT in benign insulinomas. Combination of ⁶⁸Ga-DOTA-Exendin-4 PET/CT and 68Ga-DOTANOC PET/CT can help to differentiate insulinomas and other NETs in MEN-1 and can aid in surgical planning. Malignant lesions were better identified in 68Ga-DOTANOC PET/CT however findings should be reassessed in a larger sample.