Measuring the Pancreatic β Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis

Objective: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the beta cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice. Methods: NOD mice (n = 75, 7-21 weeks old) were injected intravenously with [In-1(11)]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [In-1(11)]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the beta cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed. Results: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [In-1(11)]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM. Conclusions: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.