Visualizing pancreatic-cell mass with [11C]DTBZ
Visualizing pancreatic-cell mass with [11C]DTBZ
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DOI：
10.1016/j.nucmedbio.2006.07.002
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发表时间：
2006-10-01
影响因子：
3.1
通讯作者：
Harris, Paul Emerson
中科院分区：
文献类型：
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作者：
Simpson, Norman Ray;Souza, Fabiola;Harris, Paul Emerson
胰岛β细胞质量(BCM)影响胰岛素的总分泌量，因个体和胰岛素抵抗程度而异，并受生理和病理条件的影响。然而，朗格汉斯的胰岛似乎有胰岛素分泌的储备能力，总体而言，对胰岛素和血糖水平的评估仍然不是BCM、β细胞功能和糖尿病进展的有效衡量标准。因此，需要新的非侵入性测定BCM来为糖尿病、胰岛再生和移植的新疗法提供一个定量终点。在以前基因表达研究的基础上，我们验证了这样的假设，即用VMAT2的特异性放射性配体[C-11]二氢四苯并[11]([C-11]DTBZ)靶向VMAT2，并使用正电子发射断层扫描(PET)可以提供BCM的测量。在这份报告中，我们证明了与其正常血糖历史对照组相比，患有链脲佐菌素诱导的糖尿病的Lewis大鼠胰腺内放射性配基摄取减少。这些研究表明，使用[C-11]DTBZ和PET定量细胞中VMAT2的表达是一种无创性的纵向估计BCM变化的方法，可能在糖尿病的研究和治疗中有用。(C)2006 Elsevier Inc.保留所有权利。
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.