In Vivo Imaging of the Glucagonlike Peptide 1 Receptor in the Pancreas with 68Ga-Labeled DO3A-Exendin-4

R. K. Selvaraju, I. Velikyan, L. Johansson, Z. Wu, I. Todorov, J. Shively, F. Kandeel, O. Korsgren, O. Eriksson
2013 Journal of Nuclear Medicine  
The glucagonlike peptide 1 receptor (GLP-1R) is mainly expressed on b-cells in the islets of Langerhans and is therefore an attractive target for imaging of the b-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
more » ... keys (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 mg/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 DO3Aexendin-4 at 0.15-20 mg/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 b-cells. This result suggests that GLP-1R can be quantified in vivo, which has major implications for the prospect of imaging of native b-cells. Di abetes is one of the most common chronic diseases, and so far no cure is available for either type 1 diabetes or type 2 diabetes. Noninvasive quantification of the b-cell mass would allow assessment of the effects of new treatments aimed at b-cell regeneration, prevention of autoimmune b-cell destruction, and engraftment and survival of transplanted islets. Such quantification
doi:10.2967/jnumed.112.114066 pmid:23761918 fatcat:omgmi6t4hfdnxauvqfslc4ibq4