Visualizing pancreatic-cell mass with [11C]DTBZ

被引:102
作者
Simpson, Norman Ray
Souza, Fabiola
Witkowski, Piotr
Maffei, Antonella
Raffo, Anthony
Herron, Alan
Kilbourn, Michael
Jurewicz, Agata
Herold, Kevan
Liu, Eric
Hardy, Mark Adam
Van Heertum, Ronald
Harris, Paul Emerson
机构
[1] Columbia Univ, Sch Med, Dept Radiol, New York, NY 10032 USA
[2] Columbia Univ, Sch Med, Dept Med, New York, NY 10032 USA
[3] Columbia Univ, Sch Med, Dept Surg, New York, NY 10032 USA
[4] CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy
[5] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[6] Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA
[7] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA
[8] NIDDK, Diabet Branch, NIH, Bethesda, MD 20854 USA
关键词
diabetes; VMAT2; C-11]DTBZ;
D O I
10.1016/j.nucmedbio.2006.07.002
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 [C-11]dihydrotetrabenazine ([C-11]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 cells with the use of [C-11]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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:855 / 864
页数:10
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