Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model.
Diabetes results from an absolute or relative reduction in pancreatic beta cell mass (BCM) leading to insufficient insulin secretion and hyperglycemia. Measurement of insulin secretory capacity is currently used as a surrogate measure of BCM. However, serum insulin concentrations provide an imprecise index of BCM, and no reliable noninvasive measure of BCM is currently available. Type 2 vesicular monoamine transporters (VMAT2) are expressed in human islet beta cells, as well as in tissues of the CNS. [11C]Dihydrotetrabenazine ([11C]DTBZ) binds specifically to VMAT2 and is a radioligand currently used in clinical imaging of the brain. Here we report the use of [11C]DTBZ to estimate BCM in a rodent model of spontaneous type 1 diabetes (the BB-DP rat). In longitudinal PET studies of the BB-DP rat, we found a significant decline in pancreatic uptake of [11C]DTBZ that anticipated the loss of glycemic control. Based on comparison of standardized uptake values (SUVs) of [11C]DTBZ and blood glucose concentrations, loss of more than 65% of the original SUV correlated significantly with the development of persistent hyperglycemia. These studies suggest that PET-based quantitation of VMAT2 receptors provides a noninvasive measurement of BCM that could be used to study the pathogenesis of diabetes and to monitor therapeutic interventions.
Souza
Fabiola
F
Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA.
Simpson
Norman
N
Raffo
Anthony
A
Saxena
Chitra
C
Maffei
Antonella
A
Hardy
Mark
M
Kilbourn
Michael
M
Goland
Robin
R
Leibel
Rudolph
R
Mann
J John
JJ
Van Heertum
Ronald
R
Harris
Paul E
PE
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011869:Radioligand Assay; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine