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- Title
Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes.
- Authors
Hernandez, Reinier; Graves, Stephen A.; Gregg, Trillian; VanDeusen, Halena R.; Fenske, Rachel J.; Wienkes, Haley N.; England, Christopher G.; Valdovinos, Hector F.; Jeffery, Justin J.; Barnhart, Todd E.; Severin, Gregory W.; Nickles, Robert J.; Kimple, Michelle E.; Merrins, Matthew J.; Weibo Cai; Cai, Weibo
- 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.
- Subjects
B cells; CELL physiology; TYPE 1 diabetes; TYPE 2 diabetes; INSULIN; POSITRON emission tomography; MAGNETIC resonance imaging; LABORATORY mice; ANIMAL experimentation; CALCIUM; COMPARATIVE studies; DIABETES; ISLANDS of Langerhans; MANGANESE; RESEARCH methodology; MEDICAL cooperation; MICE; PANCREAS; RADIOPHARMACEUTICALS; RESEARCH; RESEARCH funding; EVALUATION research; CASE-control method; DISEASE progression; CELL size; PHARMACODYNAMICS; PHYSIOLOGY
- Publication
Diabetes, 2017, Vol 66, Issue 8, p2163
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-1285