title: Visualizing pancreatic beta-cell mass with [11C]DTBZ.
abstract: Beta-cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, beta-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by beta cells, with [11C]dihydrotetrabenazine ([11C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in beta cells with the use of [11C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.
authors.affiliation: Department of Radiology, Columbia University Medical School, New York, NY 10032, USA.
authors.forename: Norman Ray
authors.initials: NR
authors.lastname: Simpson
authors.forename: Fabiola
authors.initials: F
authors.lastname: Souza
authors.forename: Piotr
authors.initials: P
authors.lastname: Witkowski
authors.forename: Antonella
authors.initials: A
authors.lastname: Maffei
authors.forename: Anthony
authors.initials: A
authors.lastname: Raffo
authors.forename: Alan
authors.initials: A
authors.lastname: Herron
authors.forename: Michael
authors.initials: M
authors.lastname: Kilbourn
authors.forename: Agata
authors.initials: A
authors.lastname: Jurewicz
authors.forename: Kevan
authors.initials: K
authors.lastname: Herold
authors.forename: Eric
authors.initials: E
authors.lastname: Liu
authors.forename: Mark Adam
authors.initials: MA
authors.lastname: Hardy
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: Paul Emerson
authors.initials: PE
authors.lastname: Harris
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D010179:Pancreas / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C032811:dihydrotetrabenazine; D013747:Tetrabenazine