Validation of 111In-Exendin SPECT for the Determination of the β-Cell Mass in BioBreeding Diabetes-Prone Rats

The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of 111In-diethylenetriaminepentaacetic acid–exendin-3 (111In-exendin) in a rat model that closely mimics the development of type 1 diabetes (T1D) in humans: BioBreeding diabetes-prone (BBDP) rats. BBDP rats of 4–18 weeks of age were injected intravenously with 111In-exendin, and single-photon emission computed tomography (SPECT) images were acquired. The accumulation of the radiotracer was measured as well as the BCM and grade of insulitis by histology. 111In-exendin accumulated specifically in the islets, resulting in a linear correlation with the BCM (%) (Pearson r = 0.89, P < 0.0001, and r = 0.64 for SPECT). Insulitis did not have an influence on this correlation. These results indicate that 111In-exendin is a promising tracer to determine the BCM during the development of T1D, irrespective of the degree of insulitis.