Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes

The noninvasive measurement of functional β-cell mass would be clinically valuable for monitoring the progression of type 1 and type 2 diabetes as well as the viability of transplanted insulin-producing cells. Although previous work using MRI has shown promise for functional β-cell mass determination through voltage-dependent Ca(2+) channel (VDCC)–mediated internalization of Mn(2+), the clinical utility of this technique is limited by the cytotoxic levels of the Mn(2+) contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional β-cell mass using (52)Mn(2+) (t(1/2): 5.6 days). We investigated the whole-body distribution of (52)Mn(2+) in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of (52)Mn(2+) was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (K(ATP) channel blockers), and diazoxide (K(ATP) channel opener). In a mouse model of streptozotocin-induced type 1 diabetes, (52)Mn(2+) uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of β-cell mass from pancreatic sections. (52)Mn(2+)-PET also reported the expected increase in functional β-cell mass in the ob/ob model of pretype 2 diabetes, a result corroborated by histological β-cell mass measurements and live-cell imaging of β-cell Ca(2+) oscillations. These results indicate that (52)Mn(2+)-PET is a sensitive new tool for the noninvasive assessment of functional β-cell mass.