In vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68Ga-labeled DO3A-exendin-4.

UNLABELLED: The glucagonlike peptide 1 receptor (GLP-1R) is mainly expressed on ß-cells in the islets of Langerhans and is therefore an attractive target for imaging of the ß-cell mass. In the present study, (68)Ga-labeled exendin-4 was evaluated for PET imaging and quantification of GLP-1R in the pancreas. METHODS: Dose escalation studies of (68)Ga-labeled 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetyl (DO3A)-exendin-4 were performed in rats (organ distribution) and cynomolgus monkeys (PET/CT imaging) to determine the GLP-1R-specific tissue uptake in vivo. Pancreatic uptake (as determined by organ distribution) in healthy rats was compared with that in diabetic rats. GLP-1R occupancy in the cynomolgus pancreas was quantified with a 1-tissue-compartment model. RESULTS: In rodents, uptake in the pancreas was decreased from the baseline by up to 90% (P < 0.0001) by coadministration of DO3A-exendin-4 at 100 µg/kg. Pancreatic uptake in diabetic animals was decreased by more than 80% (P < 0.001) compared with that in healthy controls, as measured by organ distribution. GLP-1R occupancy in the cynomolgus pancreas after coinjection of DO3A-exendin-4 at 0.15-20 µg/kg ranged from 49% to 97%, as estimated by compartment modeling. CONCLUSION: These results strongly support the notion that (68)Ga-DO3A-exendin-4 uptake in the pancreas is mediated by specific receptor binding. In addition, pancreatic uptake was decreased by selective destruction of ß-cells. This result suggests that GLP-1R can be quantified in vivo, which has major implications for the prospect of imaging of native ß-cells.