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

S. Willekens, L. Joosten, O. Boerman, A. Balhuizen, D. Eizirik, M. Gotthardt and M. Brom




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.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.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.Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans.

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