Visualizing pancreatic beta-cell mass with [11C]DTBZ.
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.
Simpson
Norman Ray
NR
Department of Radiology, Columbia University Medical School, New York, NY 10032, USA.
Souza
Fabiola
F
Witkowski
Piotr
P
Maffei
Antonella
A
Raffo
Anthony
A
Herron
Alan
A
Kilbourn
Michael
M
Jurewicz
Agata
A
Herold
Kevan
K
Liu
Eric
E
Hardy
Mark Adam
MA
Van Heertum
Ronald
R
Harris
Paul Emerson
PE
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
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C032811:dihydrotetrabenazine; D013747:Tetrabenazine