Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes

Pancreatic beta -cell mass (BCM) is a major determinant of the quantity of insulin that can be secreted. BCM is markedly reduced in type 1 diabetes be cause of selective autoimmune destruction of beta -cells. Accurate assessme nt of BCM in human diabetes is limited to autopsy studies, which usually su ffer from inadequate clinical information; thus, the development of noninva sive means of BCM measurement could be important in intervention therapy. T he goal of this study was to develop such noninvasive methods for measuring BCM featuring target-specific imaging probes and to investigate whether th is technique is feasible, accurate, and predictive of BCM in normal and dia betic states. Using a beta -cell-specific monoclonal antibody IC2, modified with a radioisotope chelator for nuclear imaging, we showed that highly sp ecific binding and accumulation to beta -cells occurs after intravenous adm inistration of the probe, with virtually no binding to exocrine pancreas or stromal tissues. Furthermore, we observed a direct correlation between acc umulation of the probe with BCM in diabetic and normal animals. Nuclear ima ging of the animals that received an injection of the radioactive probe sho wed major difference in signal intensity between normal and diabetic pancre ases. The results front this study set the route for further development of imaging probes for measuring BCM that would aid in diagnosis and treatment of diabetic patients in the clinic.