% 0期刊文章%詹宁斯丹娜大卫罗素% %一个奥利维尔·巴瑞特% Gilles Tamagnan %文森特·卡罗尔%大卫Alagille %卡罗琳·帕潘托马斯•莫理% % Kenneth Marek约翰Seibyl % % T监测纹状体损失10磷酸二酯酶(PDE10A)与(18F] mni - 659和宠物:一个早期亨廷顿病(HD)进展的生物标志物。(S15.004) % D J神经病学20首页15% % P S15.004 % V 84% N % X 14补充目的:评估[18 f] mni - 659,一个高度选择性的纹状体PDE10A PET成像示踪剂,在高清年初纵向研究的生物标志物。背景:PDE10A特别表现在纹状体神经元。几项研究表明PDE10A表达式是一个敏感的标志纹状体高清病理学。横断面研究表明减少[18 f] mni - 659纹状体绑定相关临床和分子疾病严重程度的措施。设计/方法:八个高清科目(平均年龄,49.5)进行临床评估,UHDRS评级,和大脑核磁共振。组包括2科目premanifest高清2第1阶段体现高清,阶段2和4。所有的受试者都接受注射后90分钟的PET成像~ 5 mCi [18 f] mni - 659。绑定电位测定基底神经节和小脑核参考。所有接受随访[18 f] mni - 659 PET成像和临床评估大约1年之后。 RESULTS:The mean time to follow-up was 14.7 months. The mean UPDRS motor subscale score increased 3.8 points (S.D. ±7.9) and the mean total functional capacity declined 1.1 points (±2.5). Three stage 2 subjects increased to stage 3. As previously seen, the HD cohort had baseline mean [18F]MNI-659 uptake approximately 50[percnt] lower than normal. The mean annualized rates of reduction in [18F]MNI-659 uptake in caudate, putamen, and globus pallidus were 16.59[percnt] (±0.12), 6.91[percnt] (±0.04), and 5.81[percnt] (±0.07), respectively. Substantially less variability was noted in the imaging rates of change compared to clinical measures. CONCLUSIONS:[18F]MNI-659 appears to be an exceptional striatal imaging biomarker for early HD. Reductions in this PDE10A PET biomarker correlated strongly with clinical and molecular markers of early HD. Furthermore, this study demonstrates that [18F]MNI-659 appears to decline at a predictable rate in striatal nuclei across early HD. [18F]MNI-659 PET may be a valuable additional imaging biomarker in observational or interventional HD trials. Study Supported by:Molecular NeuroImaging, LLCDisclosure: Dr. Russell has received personal compensation for activities with Molecular NeuroImaging, LLC as an employee. Dr. Jennings has received personal compensation for activities with Lundbeck Research USA, Inc. and UBC Pharma. Dr. Barret has received personal compensation for activities with Molecular NeuroImaging as an employee. Dr. Tamagnan has received personal compensation for activities with Molecular NeuroImaging as an employee. Dr. Carroll has received personal compensation for activities with Molecular NeuroImaging as an employee. Dr. Alagille has received personal compensation for activities with Molecular NeuroImaging Inc. as an employee. Dr. Morley has received personal compensation for activities with Molecular NeuroImaging as an employee. Dr. Papin has received personal compensation for activities with Molecular NeuroImaging Inc. as an employee. Dr. Seibyl has received personal compensation for activities with Bayer Healthcare, GE Healthcare, and Piramal Imaging as a consultant. Dr. Marek has received personal compensation for activities with Molecular Neuroimaging, GE Healthcare, Piramal Group, Eli Lilly & Company, Merck & Co., Roche Diagnostics Corporation, Pronetha, Novartis, US WorldMeds, and nLife Therapeutics as a consultanTuesday, April 21 2015, 3:15 pm-5:00 pm %U