RT Journal Article SR Electronic T1 In Vivo Imaging of the Glucagonlike Peptide 1 Receptor in the Pancreas with 68Ga-Labeled DO3A-Exendin-4 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1458 OP 1463 DO 10.2967/jnumed.112.114066 VO 54 IS 8 A1 Ram K. Selvaraju A1 Irina Velikyan A1 Lars Johansson A1 Zhanhong Wu A1 Ivan Todorov A1 Jack Shively A1 Fouad Kandeel A1 Olle Korsgren A1 Olof Eriksson YR 2013 UL http://jnm.snmjournals.org/content/54/8/1458.abstract AB The glucagonlike peptide 1 receptor (GLP-1R) is mainly expressed on β-cells in the islets of Langerhans and is therefore an attractive target for imaging of the β-cell mass. In the present study, 68Ga-labeled exendin-4 was evaluated for PET imaging and quantification of GLP-1R in the pancreas. Methods: Dose escalation studies of 68Ga-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 68Ga-DO3A-exendin-4 uptake in the pancreas is mediated by specific receptor binding. In addition, pancreatic uptake was decreased by selective destruction of β-cells. This result suggests that GLP-1R can be quantified in vivo, which has major implications for the prospect of imaging of native β-cells.