Mapping of human cerebral sigma, receptors using positron emission tomography and [11C]SA4503
Mapping of human cerebral sigma, receptors using positron emission tomography and [11C]SA4503
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DOI：
10.1016/j.neuroimage.2006.11.055
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发表时间：
2007-03-01
期刊：
影响因子：
5.7
通讯作者：
Ishiwata, Kiichi
中科院分区：
文献类型：
--
作者：
Sakata, Muneyuki;Kimura, Yuichi;Ishiwata, Kiichi
本研究的目的是通过正电子发射断层扫描（PET）与[C-11] SA 4503建立用于绘制人脑中σ受体（cFIRs）的动力学分析。crlR被认为与各种神经和精神疾病有关。[C-11] SA 4503是最近开发的对cFIRs具有高选择性亲和力的放射性配体，我们已首次将其应用于临床研究。9例健康男性受试者在注射[C-11] SA 4503后接受了90 min动态PET扫描。除基线测量外，9例受试者中的3例在口服氟哌啶醇（一种σ受体拮抗剂）部分阻断σ IR后接受了第二次[C-11] SA 4503-PET。采用两次非线性估计的全动力学分析拟合双组织三室模型，以确定[C-11] SA 4503的结合电位（BP）和总分布容积（tDV）。还采用Logan图进行图形分析，以估计tDV。BP和tDV在11个地区的区域分布模式与先前报道的体外crlRs的分布模式一致。适当评价了氟哌啶醇减少的σ IR结合位点。从两种方法得到的tDV彼此匹配良好。Logan图提供了tDV的图像，其反映了sigma 1 R密度，并且图像中的tDV在氟哌啶醇加载后降低。此外，对血浆输入函数进行代谢物校正和未进行代谢物校正时计算的BP的比较表明，代谢物校正可以省略。我们的结论是，这种方法能够在人脑中的sigma 1 Rs的定量分析。(c)2006年爱思唯尔公司All rights reserved.
The objective of this study was to establish the kinetic analysis for mapping sigma, receptors (cFIRs) in the human brain by positron emission tomography (PET) with [C-11]SA4503. The crlRs are considered to be involved in various neurological and psychiatric diseases. [C-11]SA4503 is a recently developed radioligand with high and selective affinity for cFIRs, and we have first applied it to clinical studies. Nine healthy male subjects each underwent a dynamic 90-min PET scan after injection of [C-11]SA4503. In addition to the baseline measurement, three of the nine subjects underwent a second [C-11] SA4503-PET after partial blockade of sigma IRs by oral administration of haloperidol, a sigma receptor antagonist. Full kinetic analysis using two times nonlinear estimations was applied for fitting a two-tissue three-compartment model to determine the binding potential (BP) and total distribution volume (tDV) of [C-11]SA4503. Graphical analysis with a Logan plot was also applied for estimations of tDV. The regional distribution patterns of BP and tDV in 11 regions were compatible with those of previously reported crlRs in vitro. The reduced binding sites of sigma IRs by haloperidol were appropriately evaluated. The tDVs derived from the two methods matched each other well. The Logan plot offered images of the tDV, which reflected sigma 1R densities, and the tDV in the images decreased after haloperidol loading. Moreover, comparison of BPs calculated with and without metabolite correction for plasma input function indicated that the metabolite correction could be omitted. We concluded that this method enables the quantitative analysis of sigma 1Rs in the human brain. (c) 2006 Elsevier Inc. All rights reserved.