title: Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model.
abstract: 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.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Souza
authors.forename: Norman
authors.initials: N
authors.lastname: Simpson
authors.forename: Anthony
authors.initials: A
authors.lastname: Raffo
authors.forename: Chitra
authors.initials: C
authors.lastname: Saxena
authors.forename: Antonella
authors.initials: A
authors.lastname: Maffei
authors.forename: Mark
authors.initials: M
authors.lastname: Hardy
authors.forename: Michael
authors.initials: M
authors.lastname: Kilbourn
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Rudolph
authors.initials: R
authors.lastname: Leibel
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: Paul E
authors.initials: PE
authors.lastname: Harris
mesh_terms: 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*
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine