TY -的T1 - 10评价磷酸二酯酶(PDE10A)使用mni - 659 PET成像在亨廷顿氏舞蹈症(P07.212) JF -神经学乔-神经病学SP - P07.212 LP - P07.212六世- 80 - 7补充AU -丹娜詹宁斯盟-奥利首页维尔·巴瑞特AU -约瑟夫·弗里德曼AU -大卫罗素盟- Gilles Tamagnan盟Alagille AU -约翰Seibyl盟Kenneth Marek Y1 - 2013/02/12 UR - //www.ez-admanager.com/content/80/7_Supplement/P07.212.abstract N2 -目的:评估使用PET成像PDE10A配体的表达(18 f - mni - 659)在亨廷顿氏病(HD)和健康志愿者(高压)。背景:在亨廷顿氏病(HD)中带刺的神经元的变性和纹状体的体积损失是突出的病理结果。PDE10A纹状体中带刺的神经元中表达。抑制PDE10A已被确定为一个潜在的疾病修改高清的机制。发展mni - 659 PDE10A宠物放射性示踪剂,提供了潜在的调查PDE10A表达HD和评估药物入住率PDE10A候选疗法。设计/方法:受试者高清(n = 5)和高压(n = 5)临床特征与标准高清尺度和18 f - mni 659 PET成像完成。受试者接受5 mCi (±0。5)18 f - mni - 659和串行动态宠物投影数据收购超过1.5小时。绑定势(BPnd)测定尾状,壳核、苍白球和纹状体基于药代动力学建模使用小脑作为参考。结果:平均年龄和性别对HD 63岁(58 - 67)4 f: 1 m,和高压36岁(29-46)1 f: 4米。高清受试者轻中度疾病与手段(范围)以下尺度:总UHDRS 29.4 (18-46) UHDRS舞蹈病得分8.8 (6 - 12),UHDRS行为得分7.5(2-23)、总功能能力11(第四),独立规模92(80 - 100)和MMSE 28.4次)。18 f - mni 659意味着高清BPnd相比,高压地区:尾状HD 0.73,高压2.13;核1.41高清,高压3.74; globus pallidus HD 1.60, HV 3.52; striatum HD 1.10, HV 2.93.CONCLUSIONS: In this pilot study, 18F-MNI-659 PET shows a markedly reduced binding (60-70%) in HD compared to HV with the most pronounced reduction in the caudate, consistent with expected pathological changes in HD. These data suggest a marked reduction in PDE10A expression in mild subjects. Ongoing studies will examine MNI-659 in pre-symptomatic HD to further explore the change in PDE10A expression in HD.Supported by: In part by Pfizer, Inc.Disclosure: Dr. Jennings has received personal compensation for activities with Lundbeck. Dr. Barret has received personal compensation for activities with Molecular NeuroImaging as an employee. Dr. Friedman has received personal compensation for activities with Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc., Genzyme Corporation, Adix, Roche Diagnostics Corporation. Dr. Friedman has received research support from Teva Neuroscience, Merck & Co., Inc., EMD Serono, Schering-Plough Corporation, National Institutes of Health, Michael J. Fox Foundation, GE Healthcare and Acadia. Dr. Russell has received personal compensation for activities with Molecular NeuroImaging, LLC, Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc. as a speaker. Dr. Tamagnan has received personal compensation for activities with Molecular Neuroimaging as an employee. Dr. Alagille has nothing to disclose. Dr. Seibyl has received personal compensation for activities with Bayer Healthcare and GE healthcare as consultant. Dr. Seibyl has received compensation for serving on the board of Molecular Neuroimaging. Dr. Marek has received personal compensation for activities with GE healthcare, Eli Lilly, Astra Zeneca, Merck, and Sanofi. Dr. Marek holds stock and/or stock options in Molecualr Neuroimaging.Thursday, March 21 2013, 2:00 pm-7:00 pm ER -
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