Abstract
PurposeThe vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [18F]fluoropropyl-dihydrotetrabenazine ([18F]FP-(+)-DTBZ).ProceduresWe evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements.ResultsPancreatic BPND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4 %.ConclusionsPancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s11307-015-0888-7) contains supplementary material, which is available to authorized users.
Highlights
Real-time molecular imaging has the potential to reveal the dynamics of β cell mass (BCM) in diabetes [1, 2]
Development of hyperglycemia and β cell loss in preclinical PET studies using rodent models of diabetes [3, 4, 11, 12]; (5) dihydrotetrabenazine (DTBZ)-based positron emission tomography (PET) radiotracers bind to VMAT2 with high affinity (i.e., Kd in the subnanomolar range) [5, 12,13,14,15,16,17] and selectivity [5, 18]; and (6) DTBZ-based PET tracers are useful in longitudinal studies requiring VMAT2 quantification in the central nervous system [19]
We document the results of a crosssectional study of pancreatic VMAT2 in healthy controls and patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using PET with [18F]FP-(+)-DTBZ to estimate pancreatic biomarker of β cell mass (BCM)
Summary
Real-time molecular imaging has the potential to reveal the dynamics of β cell mass (BCM) in diabetes [1, 2]. We previously reported [11C]dihydrotetrabenazine ([11C]DTBZ) pancreatic PET uptake in humans with or without long-standing type 1 diabetes mellitus (T1DM) [20] In this latter study, pancreatic binding of [11C]DTBZ was significantly reduced in subjects with long-standing T1DM compared to healthy controls. We document the results of a crosssectional study of pancreatic VMAT2 in healthy controls and patients with T1DM and type 2 diabetes mellitus (T2DM) using PET with [18F]FP-(+)-DTBZ to estimate pancreatic BCM. To our knowledge, this is the first study evaluating VMAT2 in T2DM. This study is the first to describe the reproducibility of pancreatic [18F]FP-(+)-DTBZ uptake measurements in human pancreata
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