PET quantification of β cell mass in diabetes with [¹¹C]DTBZ

Abstract

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Objectives: The vesicular monoamine transporter type 2 (VMAT2) in CNS monoaminergic synaptic vesicles is also expressed by pancreatic β cell mass (BCM). A VMAT2 ligand, [¹¹C]DTBZ (DTBZ), has been proposed as a potential biomarker of BCM in rodent models of diabetes. We attempted PET quantification of BCM in patients with long-standing (> 20 y) type 1 diabetes (T1D), which results from immune-mediated BCM destruction.

Methods: Six T1Ds (35 ± 2 y) and 9 controls (30 ± 3 y) had dynamic abdominal DTBZ PET for 90 min (550 MBq bolus), and MRI. VMAT2 binding potential BP_ND was mapped voxel-wise by a reference tissue model (MRTM2) using renal cortex as reference tissue. 3D pancreatic regions of interest (ROIs) were identified on the BP_ND map by k-cluster analysis-based PET tissue classification algorithms and MRI. VMAT2 binding was compared between the two groups by pancreatic BP_ND in three ways: mean ROI values; voxel frequency distributions; and the functional binding capacity (FBC, defined as the sum of all voxels with BP_ND above a threshold times the voxel volume).

Results: In T1D, the ROI mean BP_ND was decreased by 14% (1.86 ± 0.05 vs. 2.14 ± 0.08; p = 0.01). The voxel BP_ND frequency distribution showed that high BP_ND signal was markedly decreased than was low signal compared with controls. FBC with BP_ND ≥ 2.5 was decreased by 70% in TID (17 ± 5 mL vs. 59 ± 7 mL; p<0.002,) and this FBC correlated with stimulated C-peptide secretion measurements (r =0.82, p < 0.002).

Conclusions: DTBZ PET may allow quantitative evaluation of pancreatic BCM noninvasively. The cause of the low BP_ND signal in TID is unclear, but may be due to underestimation of nonspecific binding in the pancreas.

Research Support: The PHS, NIH, NIDDK, 1 RO1 DK077493 and 5RO1 DK63567 (PEH), and funds provided by the Naomi Berrie Diabetes Center.