Pancreatic uptake of a beta-cell specific 68Ga-labeled GLP-1 peptide analogs in a murine model of islet amyloid-associated diabetes

Objectives Human islet amyloid polypeptide (hIAPP) deposition in pancreas islets is closely associated with the pathogenesis of type 2 diabetes. Increased deposition of hIAPP in islets and decreased β cells mass correspond with the development of type 2 diabetes. GLP-1 peptide analogs, which target glucagon-like peptide-1 receptor expressed in pancreatic β cells, have been reported useful in assessing β cell mass in STZ-induced diabetic animal models. In this study, we assessed uptake of 68Ga-labeled bicyclic GLP-1 derivative (EM2198) on a novel amyloid-deposition associated diabetic mouse model to assess the usefulness of this compound in imaging β cells mass.

Methods The hIAPP transgenic mice, which express human islet amyloid polypeptide in pancreatic cells driven by the insulin promoter and develop amyloid infiltration in the pancreas, were used to establish a diabetic animal model. Eight week old WT and transgenic mice were fed a high fat diet for 3 months. Body weight and blood glucose levels were monitored. Following injection of 130µCi of 68Ga-NOTA-EM2198, in vivo whole body PET/CT and ex vivo PET/CT imaging of the pancreas was performed on a Siemens Inveon PET/CT system.

Results After feeding on a high-fat diet for three months, the blood glucose level of wild type mice was 105±9 mg/dl, as compared to the glucose level of age-matched hIAPP mice increased to 494±81 mg/dl. The body weight was 37±6.9g for the WT mice and 28±3.8g for the hIAPP mice. In vivo PET imaging showed a higher pancreas-to-liver uptake ratio in WT mice (1.9±0.07). versus hIAPP mice (1.47±0.04, p<0.05). Ex vivo imaging confirmed the lower uptake in hIAPP mice pancreas.

Conclusions The results indicate the usefulness of 68Ga-NOTA-EM2198 as a PET tracer for noninvasive assessment of β cell mass reduction in islet amyloid-associated diabetes.