Okubo Y, Olsson H, Ito H, Lofti M, Suhara T, Halldin C, Farde L
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, S-171 76, Sweden.
Neuroimage. 1999 Dec;10(6):666-74. doi: 10.1006/nimg.1999.0502.
The Computerized Brain Atlas (CBA) transforms PET images of individual subjects into a standard brain anatomy. We have previously applied this to PET images with [(11)C]raclopride and confirmed that the D2 dopamine receptors in the striatum can be evaluated accurately with a standard brain anatomy. There is growing evidence that extrastriatal D2 receptors, in spite of their low density, have pathophysiological significance for schizophrenia. We used the CBA to explore the extrastriatal distribution of D2 receptors in 13 healthy subjects using [11C]FLB 457, a substituted benzamide with very high affinity for D2 and D3 receptors. There was good agreement between the specific binding ratios from CBA quantification of standardized images and those from region-of-interest analyses of original images. The highest levels of binding were observed in the putamen and caudate nucleus, followed by the globus pallidus and nucleus accumbens. Besides the basal ganglia, the hypothalamus and nucleus ruber also showed high levels of binding. Intermediate levels were found in the substantia nigra, nucleus subthalami, amygdala, and thalamus. Interestingly, there was very heterogeneous binding among the thalamic nuclei. The anterior and mediodorsal nuclei showed relatively high binding. The cerebral cortices showed lower levels with significant regional differences. Binding was highest in the temporal cortex and hippocampus followed by the anterior cingulate gyrus, and the parietal and frontal cortices, but was lowest in the occipital cortex. The use of CBA for analysis of [11C]FLB 457 binding makes it possible to build a normal database for the extrastriatal D2 receptors in the living human brain. The heterogeneous distribution of D2 receptors provides an attractive opportunity for new research on the pathophysiology and drug treatment of schizophrenia.
计算机化脑图谱（CBA）将个体受试者的正电子发射断层扫描（PET）图像转换为标准脑解剖结构。我们之前已将此方法应用于用[（11）C]雷氯必利的PET图像，并证实纹状体中的D2多巴胺受体可通过标准脑解剖结构准确评估。越来越多的证据表明，尽管纹状体以外的D2受体密度较低，但对精神分裂症具有病理生理学意义。我们使用CBA，利用对D2和D3受体具有非常高亲和力的取代苯甲酰胺[11C]FLB 457，探索13名健康受试者纹状体以外D2受体的分布。CBA对标准化图像的定量分析得出的特异性结合率与对原始图像的感兴趣区域分析得出的结果之间具有良好的一致性。在壳核和尾状核中观察到最高水平的结合，其次是苍白球和伏隔核。除基底神经节外，下丘脑和红核也显示出高水平的结合。在黑质、丘脑底核、杏仁核和丘脑中发现中等水平的结合。有趣的是，丘脑核团之间的结合非常不均匀。前核和背内侧核显示出相对较高的结合。大脑皮质显示出较低水平的结合，且存在显著的区域差异。颞叶皮质和海马体中的结合最高，其次是前扣带回、顶叶和额叶皮质，但枕叶皮质中的结合最低。使用CBA分析[11C]FLB 457的结合，使得有可能建立一个关于活体人脑纹状体以外D2受体的正常数据库。D2受体的不均匀分布为精神分裂症的病理生理学和药物治疗新研究提供了一个有吸引力的机会。
