Iyo M, Itoh T, Yamasaki T, Fukuda H, Inoue O, Shinotoh H, Suzuki K, Fukui S, Tateno Y
Division of Clinical Research, National Institute of Radiological Sciences, Chiba, Japan.
Neuropharmacology. 1991 Mar;30(3):207-15. doi: 10.1016/0028-3908(91)90147-4.
Central-type benzodiazepine binding sites were characterized in a single normal human subject, using positron emission tomography (PET) and the radiolabelled benzodiazepine antagonist, carbon-11 labelled flumazenil ([11C] Ro 15-1788). The subject was scanned using tracer alone and tracer plus 4 different concentrations of unlabelled Ro 15-1788, including one concentration of unlabelled Ro 15-1788, chosen to produce maximum displacement of [11C] Ro 15-1788 from specific binding sites. Concentrations of free, unmetabolized [11C] Ro 15-1788 in plasma were estimated using a simple extraction and ultrafiltration method. Radioactivity in the regional exchangeable pool in brain was estimated under non-saturation conditions from the ratio of radioactivity in brain to plasma, under saturation conditions and the kinetics of free ligand in plasma. The specific binding was, then, estimated by the difference between the total radioactivity in brain and exchangeable pool radioactivity. Scatchard analyses were performed to yield Bmax and Kd values under pseudo-equilibrium conditions, which was observed as an increase of specific binding/free with reduction in specific binding. In cerebral cortex and cerebellum, the Bmax values were about 62-73 nmol/l and the Kd values were 3.6-6 nM in the estimation of free ligand in plasma and 12-15 nM in the estimation of exchangeable pool in brain, as free in brain.
利用正电子发射断层扫描（PET）和放射性标记的苯二氮䓬拮抗剂碳-11标记氟马西尼（[11C]Ro 15-1788），对一名正常人类受试者的中枢型苯二氮䓬结合位点进行了表征。单独使用示踪剂以及示踪剂加4种不同浓度的未标记Ro 15-1788对该受试者进行扫描，其中一种未标记Ro 15-1788的浓度经选择可使[11C]Ro 15-1788从特异性结合位点的置换达到最大。采用简单的萃取和超滤方法估算血浆中游离、未代谢的[11C]Ro 15-1788的浓度。根据非饱和条件下脑内与血浆放射性之比、饱和条件下以及血浆中游离配体的动力学，估算脑内区域可交换池中的放射性。然后，通过脑内总放射性与可交换池放射性之差估算特异性结合。进行Scatchard分析以得出伪平衡条件下的Bmax和Kd值，观察到随着特异性结合减少，特异性结合/游离增加。在大脑皮层和小脑中，在估算血浆中游离配体时，Bmax值约为62 - 73 nmol/l，Kd值为3.6 - 6 nM；在估算脑内可交换池时，Bmax值约为62 - 73 nmol/l，Kd值为12 - 15 nM，脑内为游离状态。
