title: 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 beta-cells of the pancreas in association with insulin. Preclinical experiments suggested that (11)C-dihydrotetrabenazine PET-measured VMAT2 binding might serve as a biomarker of beta-cell mass. We evaluated the feasibility of (11)C-dihydrotetrabenazine PET quantification of pancreatic VMAT2 binding in healthy subjects and patients with long-standing type 1 diabetes.
  
  
  METHODS
  (11)C-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 (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).
  
  
  CONCLUSIONS
  These results suggest that (11)C-dihydrotetrabenazine PET allows quantification of VMAT2 binding in the human pancreas. However, BP(ND) and functional binding capacity appear to overestimate beta-cell mass given the near-complete depletion of beta-cell mass in long-standing type 1 diabetes, which may be due to higher nonspecific binding in the pancreas than in the renal cortex.
authors.affiliation: Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Matthew
authors.initials: M
authors.lastname: Freeby
authors.forename: Ramin
authors.initials: R
authors.lastname: Parsey
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saisho
authors.forename: Dileep
authors.initials: D
authors.lastname: Kumar
authors.forename: Norman
authors.initials: N
authors.lastname: Simpson
authors.forename: Joy
authors.initials: J
authors.lastname: Hirsch
authors.forename: Martin
authors.initials: M
authors.lastname: Prince
authors.forename: Antonella
authors.initials: A
authors.lastname: Maffei
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Peter C
authors.initials: PC
authors.lastname: Butler
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Paul E
authors.initials: PE
authors.lastname: Harris
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D007672:Kidney Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine