单次口服氟伏沙明后,人脑内Sigma-1受体的高结合率：采用[11C]SA4503的正电子发射断层扫描教程分析.docVIP

单次口服人脑内Sigma-1受体的高结合率：采用[11C]SA4503的正电子发射断层扫描 Masatomo Ishikawa, Kiichi Ishiwata, Kenji Ishii, Yuichi Kimura, Muneyuki Sakata, Mika Naganawa, Keiichi Oda, Ryousuke Miyatake, Mihisa Fujisaki, Eiji Shimizu, Yukihiko Shirayama, Masaomi Iyo and Kenji Hashimoto 背景：Sigma-1受体可能与精神病的病理生理学及一些选择性5-羟色胺再摄取抑制剂(SSRIs)的作用机制有关。在几种选择性5-羟色胺再摄取抑制剂中，氟伏沙明与sigma-1受体的亲和力最高（Ki=36nM），与sigma-1受体的亲和力较低（Ki=1893nM）。本研究考察了氟伏沙明是否与人脑内的sigma-1受体结合。 方法：使用选择性sigma-1受体配基[11C]SA4503，对动脉血样进行(PET)数据采集，以定量评价在15例健康男性志愿者体内[11C]SA4503与sigma-1受体的结合。每例受试者在随机服用单剂量氟伏沙明（50、100、150或200mg）或20mg）前后，均进行两次正电子发射断层扫描（PET）。采用2-组织3-隔室模型，计算在大脑的9个区域内[11C]SA4503的结合力。另外，我们考察了sigma-1受体(SIGMAR1)基因的功能多态性对[11C]SA4503结合力的作用。 结果：氟伏沙明可与所有脑区域的sigma-1受体结合，具有剂量依赖性，而sigma-1受体结合。不过，SIGMAR1基因多态性GC-241-240TT与结合力无关。 结论：研究表明治疗剂量的氟伏沙明可与人脑内的sigma-1受体结合。这些发现表明sigma-1受体可能在氟伏沙明的作用机制中发挥重要作用。 关键词：氟伏沙明、占领、PET、sigma-1受体、SSRI High Occupancy of Sigma-1 Receptors in the Human Brain after Single Oral Administration of Fluvoxamine:A Positron Emission Tomography Study Using[11C]SA4503 Masatomo Ishikawa, Kiichi Ishiwata, Kenji Ishii, Yuichi Kimura, Muneyuki Sakata, Mika Naganawa,Keiichi Oda, Ryousuke Miyatake, Mihisa Fujisaki, Eiji Shimizu, Yukihiko Shirayama, Masaomi Iyo,and Kenji Hashimoto Background: Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors(Ki _ 36 nM), whereas paroxetine shows low affinity (Ki _ 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. Methods: A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [11C]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [11C]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and aft