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

Diabetes. 2017 Aug;66(8):2163-2174. doi: 10.2337/db16-1285. Epub 2017 May 17.


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 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 β-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 β-cell mass from pancreatic sections. 52Mn2+-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 Ca2+ oscillations. These results indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment of functional β-cell mass.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Calcium Channels / drug effects
  • Case-Control Studies
  • Cell Size
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / diagnostic imaging
  • Disease Progression
  • Humans
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / physiology*
  • Manganese Compounds / pharmacology*
  • Mice
  • Pancreas / cytology
  • Pancreas / diagnostic imaging
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacology*
  • Streptozocin


  • Calcium Channels
  • Manganese Compounds
  • Radiopharmaceuticals
  • Streptozocin