Strain Differences Determine the Suitability of Animal Models for Noninvasive In Vivo Beta Cell Mass Determination with Radiolabeled Exendin

PURPOSE: Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [(111)In]exendin is a promising agent for in vivo beta cell imaging, but tracer testing has been hampered by the lack of well-defined rodent models. PROCEDURES: Biodistribution and pancreatic uptake of [(111)In]exendin were compared in rats and mice. In selected models, the amount of [(111)In]exendin accumulation in the pancreas and other organs was determined using a model of alloxan-induced beta cell loss. GLP-1R expression levels were analyzed by RT-PCR and immunohistochemistry. RESULTS: Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas-to-background ratios for noninvasive BCM determination. Mice displayed receptor-mediated [(111)In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue. CONCLUSIONS: Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-016-0936-y) contains supplementary material, which is available to authorized users.