Studies on Quantitative Analysis of Dopamine Receptor Function in Brain.

为了建立人脑中多巴胺受体的定量测量方法，我们考察了基于放射性配体动力学行为的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)技术，使用2‘-碘胡椒酮(2’-isp)和碘苯并呋喃(IBF)这两种与多巴胺D2受体结合的碘-123标记的放射性配体。给正常人静脉注射后，进行连续SPECT显像，间歇采血，分析血液代谢物。2‘-isp和IBF与纹状体多巴胺受体均表现出选择性和可逆性结合。在2‘-isp中，纹状体摄取在给药后1小时达到最大值，此后逐渐下降。纹状体与大脑皮质的比值(Str/Cx)作为受体结合的简单定量指标，在2~4小时内几乎保持不变，提示该指标可作为临床研究中评价受体结合的一个简单参数。IBF在纹状体中的摄取速度更快，从非特异性结合部位的清除速度更快，导致Str/Cx比值比2‘-ISP更大。利用系列SPECT数据对IBF进行脑室分析，计算的纹状体结合势与Str/Cx比值有很好的一致性，但Str/Cx比值的时间依赖性变化值得注意。结果表明，拟平衡状态下特异性结合与非特异性结合的比值可能存在随时间变化的问题，尽管它可以作为临床上的一个简单参数。

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.