PET ANALYSIS OF D1 DOPAMINE RECEPTORS IN SCHIZOPHRENIA

应用程序的广泛长期目标是增加 精神分裂症的病理生理机制知识。 其具体目的是开发一种PET扫描程序，用于定量 DL-的分布、密度和亲和力特性的研究 脑内主要基底节和其他区域的多巴胺受体 活着的人脑。方法论将被应用于比较 药物未成熟的精神分裂症患者的DL受体特征 和健康的志愿者。精神分裂症患者的化学治疗 不同类型的抗精神病药物也将在以下方面进行审查 与DL-多巴胺受体特性有关。DL-多巴胺受体的变化 长期服用抗精神病药物期间和治疗后的特点 对这种待遇的决定也将进行审查。对于PET来说- 扫描程序高效、选择性的DL-多巴胺受体 将使用拮抗剂SCH 23390。我们的初步结果表明 该配体(1)对DL受体有很高的选择性，(2)有很高的选择性 体内特异性结合与非特异性结合的比率和(3)显示 关于结合的立体特异性。这种配基已经被证明是 静脉给药后具有良好的动力学特性 用于定量PET扫描分析或以Bmax为单位的DL受体特性 和KD。我们的初步结果表明11-C-SCH 23390是饱和的 与人壳核中的DL受体结合。BMax-顺序中的值 可获得25pmol/g的组织。这些值与我们的 在使用~3H标记配体(Eh-SCH)的初步实验中获得 23390)在人死后获得的壳核中。该项目旨在 比较与DL-多巴胺受体相关的PET扫描结果 特性与在体外条件下获得的特性 精神分裂症患者和健康志愿者。该项目还旨在 开发一种基于使用的定量放射自显影技术 11-C标记的配体。PET扫描实验将使用我们的 新的高分辨率PET摄像系统，允许分辨率 活体人脑中约5毫米大小的结构。这 新的摄像系统可能允许对DL-多巴胺受体进行定量 几个边缘和皮质脑区也有特征，如 活人的大脑干核团(黑质)也是如此。 研究对象。

The broad long-term objectives of the application is to increase knowledge concerning pathophysiological mechanisms in the schizophrenias. The specific aim is to develop a PET-scan procedure for quantitative studies on the distribution, density and affinity characteristics of Dl- dopamine receptors in the major basal ganglia and other regions in the living human brain. The methodology will be applied to a comparison between Dl receptor characteristics in drug naive schizophrenic patients and healthy volunteers. Schizophrenic patients treated with chemically different types of antipsychotic drugs will also be examined with regard to Dl-dopamine receptor characteristics. Changes in Dl-dopamine receptor characteristics during long-term neuroleptic treatment and after the determination of such treatment will also be examined. For the PET- scanning procedure the highly potent and selective Dl-dopamine receptor antagonist SCH 23390 will be used. Our preliminary results indicate that this ligand, (1) has a high selectivity for Dl receptors, (2) has a high ratio of specific to non specific binding in vivo and (3) exhibits stereospecificity with regard to binding. This ligand has been shown to have excellent kinetic properties after intravenous administration to man for quantitative PET-scan analysis or Dl receptor characteristics as Bmax and Kd. Our preliminary results indicate saturability of 11-C-SCH 23390 binding to Dl receptors in the human putamen. Bmax-values in the order of 25 pmol/g tissue were obtained. These values are similar to those we obtained in preliminary experiments using the 3H-labelled ligand (eH-SCH 23390) in human putamen obtained postmortem. The project aims at comparing PET-scan results with regard to Dl-dopamine receptor characteristics with those obtained during in vitro conditions in schizophrenic patients and healthy volunteers. The project also aims at developing a quantitative autoradiographic technique based on the use of 11-C-labelled ligands. PET-scan experiments will be performed using our new high resolution PET camera system allowing the resolution of structures in the living human brain in the order of about 5 mm. This new camera system may allow quantitation of Dl-dopamine receptor characteristics also in several limbic and cortical cerebral areas as well as in large brain stem nuclei (substantia nigra) of living human subjects.