KINETIC-ANALYSIS OF CENTRAL [C-11] RACLOPRIDE BINDING TO D2-DOPAMINE RECEPTORS STUDIED BY PET - A COMPARISON TO THE EQUILIBRIUM-ANALYSIS
KINETIC-ANALYSIS OF CENTRAL [C-11] RACLOPRIDE BINDING TO D2-DOPAMINE RECEPTORS STUDIED BY PET - A COMPARISON TO THE EQUILIBRIUM-ANALYSIS
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DOI：
10.1038/jcbfm.1989.98
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发表时间：
1989-10-01
影响因子：
6.3
通讯作者：
HALLDIN, C
中科院分区：
文献类型：
--
作者：
FARDE, L;ERIKSSON, L;HALLDIN, C
[11C]Raclopride与中枢d2 -多巴胺受体的结合先前已通过正电子发射断层扫描（PET）进行了研究。基于快速发生的结合平衡，饱和度分析已被开发用于确定受体密度（Bmax）和亲和力（Kd）。对于用其他配体获得的PET测量结果的分析，使用了动力学三室模型。在本研究中，通过对三名健康受试者的四次PET实验数据进行动力学和平衡分析，进一步分析了[11C]raclopride的脑摄取。首先确定了区域CBV。在第二和第三个实验中，分别使用高比活性和低比活性的[11C]- raclopride。在第四个实验中，使用[11C]raclopride对映体[11C]FLB472检测脑内游离放射性配体和非特异性结合的浓度。使用自动血液采样系统测量动脉血液中的放射性。通过动力学分析还可以确定[11C]raclopride结合的Bmax和Kd值。正如理论上预期的那样，这些值与平衡分析得到的值相似。此外，动力学分析允许分别测定缔合和解离速率常数，分别为kon和Koff。对[11C]雷氯pride和[11C]FLB472在缺乏特异性d2 -多巴胺受体结合的脑区摄取的检查表明，在研究的剂量范围内，第四室的摄取是可逆的、非立体选择性的和不饱和的。
[11C]Raclopride binding to central D2-dopamine receptors in humans has previously been examined by positron emission tomography (PET). Based on the rapid occurrence of binding equilibrium, a saturation analysis has been developed for the determination of receptor density (Bmax) and affinity (Kd). For analysis of PET measurements obtained with other ligands, a kinetic three-compartment model has been used. In the present study, the brain uptake of [11C]raclopride was analyzed further by applying both a kinetic and an equilibrium analysis to data obtained from four PET experiments in each of three healthy subjects. First regional CBV was determined. In the second and third experiment, [11C]- raclopride with high and low specific activity was used. In a fourth experiment, the [11C]raclopride enantiomer [11C]FLB472 was used to examine the concentration of free radioligand and nonspecific binding in brain. Radioactivity in arterial blood was measured using an automated blood sampling system. Bmax and Kd values for [11C]raclopride binding could be determined also with the kinetic analysis. As expected theoretically, those values were similar to those obtained with the equilibrium analysis. In addition, the kinetic analysis allowed separate determination of the association and dissociation rate constants, kon and Koff, respectively. Examination of [11C]raclopride and [11C]FLB472 uptake in brain regions devoid of specific D2-dopamine receptor binding indicated a fourth compartment in which uptake was reversinble, nonstereoselective, and nonsaturable in the dose range studied.