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

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