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

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

Author information

1
Department of Medical Physics, University of Wisconsin-Madison, Madison, WI.
2
Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, WI.
3
Program in Biophysics, University of Wisconsin-Madison, Madison, WI.
4
Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI.
5
Center for Nuclear Technologies, Technical University of Denmark, Roskilde, Denmark.
6
Department of Chemistry, Michigan State University, East Lansing, MI.
7
William S. Middleton Memorial Veterans Hospital, Madison, WI.
8
Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, WI merrins@wisc.edu wcai@uwhealth.org.
9
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI.
10
Department of Medical Physics, University of Wisconsin-Madison, Madison, WI merrins@wisc.edu wcai@uwhealth.org.
11
Department of Radiology, University of Wisconsin-Madison, Madison, WI.

Abstract

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.

PMID:
28515126
PMCID:
PMC5521871
DOI:
10.2337/db16-1285
[Indexed for MEDLINE]
Free PMC Article

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