Farde L, Eriksson L, Blomquist G, Halldin C
Department of Psychiatry and Psychology, Karolinska Institutet, Stockholm, Sweden.
J Cereb Blood Flow Metab. 1989 Oct;9(5):696-708. doi: 10.1038/jcbfm.1989.98.
[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. Radio-activity 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 reversible, nonstereoselective, and nonsaturable in the dose range studied.
此前已通过正电子发射断层扫描（PET）对人体中[11C]雷氯必利与中枢D2 - 多巴胺受体的结合情况进行了研究。基于结合平衡的快速达成，已开发出一种饱和分析法来测定受体密度（Bmax）和亲和力（Kd）。对于用其他配体获得的PET测量值的分析，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每人进行的四项PET实验所获数据应用动力学分析和平衡分析，进一步分析了[11C]雷氯必利在大脑中的摄取情况。首先测定区域脑血容量（CBV）。在第二项和第三项实验中，分别使用了高比活度和低比活度的[11C] - 雷氯必利。在第四项实验中，使用[11C]雷氯必利对映体[11C]FLB472来检测大脑中游离放射性配体的浓度和非特异性结合。使用自动血液采样系统测量动脉血中的放射性。[11C]雷氯必利结合的Bmax和Kd值也可以通过动力学分析来确定。正如理论上预期的那样，这些值与通过平衡分析获得的值相似。此外，动力学分析分别允许单独测定缔合速率常数kon和解离速率常数koff。对缺乏特异性D2 - 多巴胺受体结合的脑区中[11C]雷氯必利和[11C]FLB472摄取的检查表明，存在第四个房室，在该房室中摄取是可逆的、非立体选择性的，并且在所研究的剂量范围内是不饱和的。
