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 channel (VDCC)-mediated internalization of Mn , the clinical utility of this technique is limited by the cytotoxic levels of the Mn contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional β-cell mass using Mn ( : 5.6 days). We investigated the whole-body distribution of Mn in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of Mn was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (K channel blockers), and diazoxide (K channel opener). In a mouse model of streptozotocin-induced type 1 diabetes, Mn uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of β-cell mass from pancreatic sections. Mn -PET also reported the expected increase in functional β-cell mass in the / model of pretype 2 diabetes, a result corroborated by histological β-cell mass measurements and live-cell imaging of β-cell Ca oscillations. These results indicate that Mn -PET is a sensitive new tool for the noninvasive assessment of functional β-cell mass.