11C-Dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls

Abstract

Type 2 vesicular monoamine transporter (VMAT2), found in the brain, is also expressed by β-cells of the pancreas in association with insulin. Preclinical experiments suggested that 11C-dihydro-tetrabenazine PET-measured VMAT2 binding might serve as a biomarker of β-cell mass. We evaluated the feasibility of 11C-dihydrotetrabenazine PET quantification of pancreatic VMAT2 binding in healthy subjects and patients with long-standing type 1 diabetes. Methods; 11C-Dihydrotetrabenazine PET was performed on 6 patients and 9 controls. VMAT2 binding potential (SP ND) was estimated voxelwise by using the renal cortex as reference tissue. As an index of total pancreatic VMAT2, the functional binding capacity (the sum of voxel SP ND x voxel volume) was calculated. Pancreatic BP ND functional binding capacity, and stimulated insulin secretion measurements were compared between groups. Results: The pancreatic mean BP ND was decreased in patients (1.86± 0.05) to 86% of control values (2.14 plusmn; 0.08) (P = 0.01). In controls, but not in patients, SP ND correlated with stimulated insulin secretion (r 2 = 0.50, P = 0.03). The average functional binding capacity was decreased by at least 40% in patients (P = 0.001). The changes in functional binding capacity and BP ND were less than the near-complete loss of stimulated insulin secretion observed in patients (P = 0.001). Conclusion: These results suggest that 11C-dihydrotetrabenazine PET allows quantification of VMAT2 binding in the human pancreas. However, BP ND and functional binding capacity appear to overestimate β-cell mass given the near-complete depletion of p-cell mass in long-standing type 1 diabetes, which may be due to higher nonspecific binding in the pancreas than in the renal cortex. COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.