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 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.
Goland
Robin
R
Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA.
Freeby
Matthew
M
Parsey
Ramin
R
Saisho
Yoshifumi
Y
Kumar
Dileep
D
Simpson
Norman
N
Hirsch
Joy
J
Prince
Martin
M
Maffei
Antonella
A
Mann
J John
JJ
Butler
Peter C
PC
Van Heertum
Ronald
R
Leibel
Rudolph L
RL
Ichise
Masanori
M
Harris
Paul E
PE
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*
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine