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¹¹C-Dihydrotetrabenazine PET of the Pancreas in Subjects with Long-Standing Type 1 Diabetes and in Healthy Controls

Robin Goland^*,1, Matthew Freeby^*,1, Ramin Parsey^*,2, Yoshifumi Saisho³, Dileep Kumar^2,4, Norman Simpson², Joy Hirsch⁴, Martin Prince⁴, Antonella Maffei^5,6, J. John Mann², Peter C. Butler³, Ronald Van Heertum⁴, Rudolph L. Leibel¹, Masanori Ichise^,4 and Paul E. Harris^,1,6

¹ Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York; ² Department of Psychiatry of Columbia University Medical Center, New York, New York; ³ Larry Hillblom Islet Research Center, University of California, Los Angeles, California; ⁴ Department of Radiology of Columbia University Medical Center, New York, New York; ⁵ Institute of Genetics and Biophysics "Adriano Buzzati-Traverso," CNR, Naples, Italy; and ⁶ Department of Medicine of Columbia University Medical Center, New York, New York

Correspondence: For correspondence or reprints contact: Paul E. Harris, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 W. 168th St., New York, NY, 10032. E-mail: peh1{at}columbia.edu

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-dihydrotetrabenazine 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 (BP_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 BP_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 ± 0.08) (P = 0.01). In controls, but not in patients, BP_ND correlated with stimulated insulin secretion (r² = 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 β-cell mass in long-standing type 1 diabetes, which may be due to higher nonspecific binding in the pancreas than in the renal cortex.

Key Words: β-cell mass • diabetes • VMAT2 • ¹¹C-dihydrotetrabenazine • PET

^* Contributed equally to this work.

Contributed equally to this work.

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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