Mishina Masahiro, Ishiwata Kiichi, Kimura Yuichi, Naganawa Mika, Oda Keiichi, Kobayashi Shiro, Katayama Yasuo, Ishii Kenji
Neurological Institute, Nippon Medical School Chiba-Hokusoh Hospital, Imba-gun, Chiba-ken 270-1694, Japan.
Synapse. 2007 Sep;61(9):778-84. doi: 10.1002/syn.20423.
Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain.
腺苷A(2A)受体（A2AR）被认为与多巴胺D(2)受体相互作用。选择性A2AR拮抗剂作为帕金森病的治疗方法已引起关注。在本研究中，我们使用正电子发射断层扫描（PET）和[7-甲基-(11)C]-(E)-8-(3,4,5-三甲氧基苯乙烯基)-1,3,7-三甲基黄嘌呤（[(11)C]TMSX）研究了A2ARs在活体人脑中的分布。我们招募了5名正常男性受试者。进行了一系列60分钟的动态PET扫描，并在扫描过程中采集动脉血以测量母体化合物和标记代谢物的放射性。为每个受试者在PET图像上的小脑、脑干、丘脑、尾状核头部、前壳核和后壳核、额叶、颞叶、顶叶、枕叶以及后扣带回放置直径为10毫米的圆形感兴趣区。使用双组织三室模型来估计代谢物校正后的血浆与[(11)C]TMSX组织时间活性之间的K(1)、k(2)、k(3)和k(4)。结合潜能（BP）在前壳核（1.25）和后壳核（1.20）中最大，其次在尾状核头部（1.05）和丘脑（1.03）中较大，而在大脑皮层尤其是额叶（0.46）中较小。[(11)C]TMSX PET显示纹状体中的BP最大，正如死后和非人类研究报道的那样，A2ARs在纹状体中富集，但与其他哺乳动物相比，[(11)C]TMSX在丘脑中的结合相对较大。迄今为止，[(11)C]TMSX是唯一一种有前景的PET配体，可用于临床在活体人脑中绘制A2ARs图谱。
