SPECT IMAGING OF 5HT1A RECEPTOR

大脑5-羟色胺受体与精神疾病有关， 特别是14个人的抑郁、焦虑和药物滥用 大脑中发现的5-羟色胺受体亚型--5HT-1A 受体是非典型抗焦虑药物的直接靶点 丁螺环酮与抗抑郁药物的间接靶点测定 SPECT监测活体脑内该受体的可行性 成像，我们研究了路100635，路100635是Re的类似物 一种芳基哌嗪，以前已被确定为PET配体 大脑5HT1a 5-羟色胺受体，以努力优化 这些金属螯合类似物的亲和力和脑摄取 用受体之间的各种连接物合成化合物 人血清白蛋白的结合部分和两种N2S2螯合体系的体外测定 在大脑额叶皮质进行复合体实验。 [3H]8-OH-DPAT a 5HT1a配体和[~3H]7-OH-DPAT标记D3 几种化合物对多巴胺受体的纳摩尔亲和力 5HT1a受体和一种化合物对D3多巴胺有效 受体对脑摄取和生物分布的进一步研究 计划在小型哺乳动物物种中成功地进行大脑成像 带有氚标记探针的多巴胺转运体可能延伸到 其他与治疗或诊断相关的蛋白质艾伦·J·费施曼， 马萨诸塞州放射学核医学系医学博士 马萨诸塞州波士顿综合医院将开发和评估新型PET和 SPECT显像剂作为帕金森病患者多巴胺神经元的标志物 疾病和其他脑部疾病进行临床试验 阿托品用于确定候选可卡因的大脑占有率 用于确定慢性给药的疗效的药物 用于评估大脑的脑多巴胺系统的候选药物 一种新的抗帕金森病候选药物的占有率将开发新的 马萨诸塞州综合医院氚试剂Ali Bonab，PhD 波士顿，马萨诸塞州纳特·阿尔伯特，马萨诸塞州总医院波士顿， MA将开发用于定量多巴胺转运体的方法 脑部的PET成像安娜-利萨·布朗内尔，博士 马萨诸塞州波士顿马萨诸塞州总医院放射科将进行PET 用新化合物和其他化合物进行成像研究，以探索 可卡因的目标Peter C Meltzer，PhD，Organix，Inc.Paul Blundell， 博士将合成和评价作为单胺探针的新型硫烷 转运蛋白作为可卡因的显像剂和治疗剂 药物和帕金森氏病开发新的锶制剂 Aloke duta，PhD，Organix，Inc.将开发有效和选择性的GBR 多巴胺转运蛋白的类似物阿伦·G·琼斯，哈佛大学博士 哈佛医学院阿什法克·马哈茂德博士 开发脑多巴胺和5-羟色胺的氚显像剂 系统艾伦·戴维森，麻省理工学院博士 开发脑多巴胺和5-羟色胺的氚显像剂 系统杰克·伯格曼博士，马萨诸塞州贝尔蒙特麦克莱恩医院 慢性可卡因对脑内多巴胺系统的影响 豪利特，密苏里州圣路易斯大学Ph D调查 大麻素/多巴胺激动剂相互作用评估疗效 大麻素拮抗剂苏珊·阿马拉、马克·桑德斯、Vollum的潜力 波特兰研究所，或确定新药对电流的影响 在转基因细胞中，苏珊·乔治，医学博士，大学 多伦多大学的Brian O‘Dowd博士测量 非胺类物质对体内细胞外多巴胺水平的影响 霍夫曼，Ph D NIH将开发多巴胺的点突变 运输者菲利普·西曼，医学博士，博士将提出新的假设 抗多动症药物的作用机制

Brain serotonin receptors are implicated in psychiatric disorders, particularly depression, anxiety and substance abuse Of the 14 subtypes of serotonin receptors identified in brain, the 5HT-1A receptor is a direct target of the atypical anti-anxiety drug buspirone and an indirect target of antidepressant drugs To determine the feasibility of monitoring this receptor in living brain by SPECT imaging, we investigated rhenium analogues of WAY 100635 WAY 100635 is an aryl piperazine that previously has been identified as a PET ligand for brain 5HT1A serotonin receptors In an effort to optimize the affinity and brain uptake of these metal-chelated analogues, several compounds were synthesized with various linkers between the receptor binding moiety and two N2S2 chelate systems In vitro assays of the complexes were conducted in frontal cortex of brain using [3H]8-OH-DPAT a 5HT1A ligand and [3H]7-OH-DPAT to label the D3 dopamine receptor Several compounds displa yed nanomolar affinity for the 5HT1A receptor and one compound was potent at the D3 dopamine receptor Further research on brain uptake and biodistribution is planned in small mammalian species Our successful imaging of the brain dopamine transporter with technetium-labeled probes may extend to other proteins of therapeutic or diagnostic relevance Alan J Fischman, MD, Ph D Department of Nuclear Medicine, Radiology, Massachusetts General Hospital, Boston, MA To develop and evaluate novel PET and SPECT imaging agents as markers for dopamine neurons in Parkinson's disease and other brain disorders To conduct clinical trials with altropane To determine brain occupancy of candidate cocaine medications To determine the effects of chronic administration of candidate medications on brain dopamine systems To evaluate the brain occupancy pf a novel candidate antiparkinsonian drug To develop novel technetium agents Ali Bonab, Ph D , Massachusetts General Hospital Boston, MA Nat Alpert, Ph D , Massachusetts General Hospital Boston, MA To develop methods for quantifying the dopamine transporter using PET imaging of brain Anna-Liisa Brownell, Ph D , Department of Radiology ,Massachusetts General Hospital ,Boston, MA To conduct PET imaging studies with novel and other compounds, for probing the targets of cocaine Peter C Meltzer, Ph D , Organix, Inc Paul Blundell, Ph D To synthesize and evaluate novel tropanes as probes for monoamine transporters, as imaging agents and as therapeutics for cocaine medications and Parkinson's disease To develop novel technetium agents Aloke Dutta, Ph D , Organix, Inc To develop potent and selective GBR analogs for the dopamine transporter Alun G Jones, Ph D , Harvard Medical School Ashfaq Mahmood, Ph D , Harvard Medical School To develop technetium imaging agents for brain dopamine and serotonin systems Alan Davison, Ph D , Massachusetts Institute of Technology To develop technetium imaging agents for brain dopamine and serotonin systems Jack Bergman, Ph D , McLean Hospital, Belmont, MA To measure the effects of chronic cocaine on dopamine systems in brain Allyn C Howlett, Ph D St Louis University, St Louis MO To investigate cannabinoid/dopamine agonists interaction To assess therapeutic potential of cannabinoid antagonists Susan Amara, Mark Sonders, Vollum Institute, Portland OR To determine effects of novel drugs on currents in cells transfected with transporters Susan George, M D , University of Toronto Brian O'Dowd, Ph D ,University of Toronto To measure effects of non-amines on extracellular dopamine levels in vivo Beth Hoffman, Ph D NIH To develop point mutations on the dopamine transporter Philip Seeman, M D , Ph D To develop novel hypotheses on mechanism of action of anti-hyperactivity medications