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

ABSTRACT: The noninvasive measurement of functional ?-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 ?-cell mass determination through voltage-dependent Ca2+ channel (VDCC)-mediated internalization of Mn2+, the clinical utility of this technique is limited by the cytotoxic levels of the Mn2+ contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional ?-cell mass using 52Mn2+ (t1/2: 5.6 days). We investigated the whole-body distribution of 52Mn2+ in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of 52Mn2+ was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (KATP channel blockers), and diazoxide (KATP channel opener). In a mouse model of streptozotocin-induced type 1 diabetes, 52Mn2+ uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of ?-cell mass from pancreatic sections. 52Mn2+-PET also reported the expected increase in functional ?-cell mass in the ob/ob model of pretype 2 diabetes, a result corroborated by histological ?-cell mass measurements and live-cell imaging of ?-cell Ca2+ oscillations. These results indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment of functional ?-cell mass.

SUBMITTER: Hernandez R 

PROVIDER: S-EPMC5521871 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other