Farde L, Suhara T, Nyberg S, Karlsson P, Nakashima Y, Hietala J, Halldin C
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Psychopharmacology (Berl). 1997 Oct;133(4):396-404. doi: 10.1007/s002130050420.
We recently developed [11C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D2-dopamine receptors in vitro. The aim of the present exploratory study was to examine the anatomical distribution of [11C]FLB 457 binding in the human brain and to determine extrastriatal D2-receptor occupancy in antipsychotic drug-treated patients. [11C]raclopride was used to obtain reference values for D2-dopamine receptor occupancy in the putamen. After IV injection of [11C]FLB 457 there was a high concentration of radioactivity, not only in the caudate putamen but also in the thalamus and the temporal cortex. The concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. Pretreatment with haloperidol and fluphenazine indicated that [11C]FLB 457 binding in extrastriatal regions to a high degree represent specific binding to D2-dopamine receptors. The D2-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [11C]raclopride in the putamen. The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man.
我们最近研发了[11C]FLB 457，这是一种取代苯甲酰胺，在体外对D2 - 多巴胺受体具有20 pM的极高亲和力。本探索性研究的目的是检查[11C]FLB 457在人脑内的结合解剖分布，并确定抗精神病药物治疗患者纹状体以外区域的D2受体占有率。[11C]雷氯必利用于获取壳核中D2 - 多巴胺受体占有率的参考值。静脉注射[11C]FLB 457后，不仅尾状核壳核，而且丘脑和颞叶皮质都有高浓度的放射性。额叶皮质、黑质和丘脑中的放射性浓度略高于小脑。氟哌啶醇和氟奋乃静预处理表明，[11C]FLB 457在纹状体以外区域的结合在很大程度上代表了与D2 - 多巴胺受体的特异性结合。抗精神病药物治疗患者丘脑和颞叶皮质中的D2占有率与用[11C]雷氯必利在壳核中测定的水平相同。该研究表明，[11C]FLB 457具有对人体D2 - 多巴胺受体进行定量PET检查的潜力。
