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Studies on Quantitative Analysis of Dopamine Receptor Function in Brain.

脑中多巴胺受体功能的定量分析研究。

基本信息

批准号：
08457242
负责人：
YONEKURA Yoshiharu
金额：
$ 3.33万
依托单位：
Fukui Medcal School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457242/
关键词：
Neuroreceptor dopamine image analysis SPECT brain function

项目摘要

In order to establish the methods for quantitative measurement of dopamine receptors in human brain, we have examined the various approaches based on the mathematical modeling of the kinetic behavior of the radioligands for development of simple methods to be used for clinical studies. The study was performed with single photon emission computed tomography (SPECT) using two iodine-123 labeled radioligands which bind to dopamine D2 receptors, 2'-iodospiperone (2'-ISP) and iodobenzofuran (IBF). Following the intravenous injection to the normal subjects, serial SPECT imaging was performed with intermittent blood sampling for the analysis of blood metablites. Both 2'-ISP and IBF showed selective and reversible binding to the striatal dopamine receptors. In 2'-ISP,the striatal uptake reached maximum value at one hour after the administration, and decreased gradually thereafter. Striatum to cerebral cortex (Str/Cx) ratio obtained as a simple quantitative index of receptor binding revealed nearly constant between 2 and 4 hours, suggesting that this index can be used as a simple parameter to evaluate the receptor binding in clinical studies. IBF showed more rapid uptake in the striatum and faster clearance from the nonspecific binding site, resulting in the greater valus for Str/Cx ratio than 2'-ISP.Binding potential in the striatum calculated by the compartment analysis of IBF using the serial SPECT data and the arterial blood activity demonstrated a good agreement with Str/Cx ratio, but the time dependent changes in Str/Cx ratio was noted.The results suggested that the ratio of specific binding to nonspecific binding during the pseudo-equilibrium state may be of some problem for the time dependent changes of the value although it can be used noninvasively as a simple parameter in clinical settings.

为了建立定量测定人脑多巴胺受体的方法，我们研究了基于放射性配体动力学行为数学模型的各种方法，以开发用于临床研究的简单方法。本研究采用单光子发射计算机断层扫描（SPECT）进行，使用两种碘-123标记的放射性配体，结合多巴胺D2受体，2 '-碘螺哌隆（2'-ISP）和碘苯并呋喃（IBF）。正常受试者静脉注射后，间歇采血进行SPECT显像，分析血液代谢物。2 '-ISP和IBF都显示出与纹状体多巴胺受体的选择性和可逆性结合。在2 '-ISP中，纹状体摄取在给药后1h达到最大值，此后逐渐下降。纹状体与大脑皮质（Str/Cx）的比值作为受体结合的一个简单的定量指标，在2 - 4小时之间几乎保持不变，表明该指标可以作为一个简单的参数，以评估受体结合在临床研究中。结果表明，IBF在纹状体的摄取速度快，从非特异性结合部位的清除速度快，Str/Cx比值的值大于2 ′-ISP。结果表明，在假手术过程中，特异性结合与非特异性结合的比值随时间的变化而变化，而特异性结合与非特异性结合的比值随时间的变化而变化。平衡状态对于该值的时间依赖性变化可能存在一些问题，尽管它可以在临床环境中无创地用作简单参数。