Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging([^(18)F]AV-133)  

作　　者：Yajing Liu Feng Yue Rongping Tang Guoxian Tao Xiaomei Pan Lin Zhu Hank F.Kung Piu Chan 

机构地区：[1]Department of Neurobiology, Xuanwu Hospital of Capital Medical University [2]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital of Capital Medical University [3]Beijing Key Laboratory on Parkinson's Disease [4]Wincon Theracells Biotechnologies Inc. [5]Key Laboratory of Radiopharmaceuticals, Beijing Normal University [6]Department of Radiology, University of Pennsylvania

出　　处：《Neuroscience Bulletin》2014年第3期409-416,共8页神经科学通报（英文版）

基　　金：supported by grants from the Ministry of Science and Technology of China (2012AA02A514, 2011CB504101);a Science Research and Technology Development Project from the Bureau of Science and Technology of Nanning, China (201001010A);the China Postdoctoral Science Foundation (20110490452);the Beijing Postdoctoral Research Activity Foundation (2011ZZ-07);the Open Fund for the Key Laboratory on Neurodegenerative Disease of the Ministry of Education (2012SJBX01)

摘　　要：The 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine （MPTP）-induced parkinsonism model, particularly in non-human primates, remains the gold-standard for studying the pathogenesis and assessing novel therapies for Parkinson＇s disease. However, whether the loss of dopaminergic neurons in this model is progressive remains controversial, mostly due to the lack of objective in vivo assessment of changes in the integrity of these neurons. In the present study, parkinsonism was induced in cynomolgus monkeys by intravenous administration of MPTP （0.2 mg/kg） for 15 days; stable parkinsonism developed over 90 days, when the symptoms were stable. Noninvasive positron emission tomographic neuroimaging of vesicular monoamine transporter 2 with 9-[18F] fluoropropyl-（＋）-dihydrotetrabenazine （[18F]AV-133） was used before, and 15 and 90 days after the beginning of acute MPTP treatment. The imaging showed evident progressive loss of striatal uptake of [18SF]AV-133. The dopaminergic denervation severity had a significant linear correlation with the clinical rating scores and the bradykinesia subscores. These findings demonstrated that [18F]AV-133 PET imaging is a useful tool to noninvasively evaluate the evolution of monoaminergic terminal loss in a monkey model of MPTP-induced parkinsonism.The 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine （MPTP）-induced parkinsonism model, particularly in non-human primates, remains the gold-standard for studying the pathogenesis and assessing novel therapies for Parkinson＇s disease. However, whether the loss of dopaminergic neurons in this model is progressive remains controversial, mostly due to the lack of objective in vivo assessment of changes in the integrity of these neurons. In the present study, parkinsonism was induced in cynomolgus monkeys by intravenous administration of MPTP （0.2 mg/kg） for 15 days; stable parkinsonism developed over 90 days, when the symptoms were stable. Noninvasive positron emission tomographic neuroimaging of vesicular monoamine transporter 2 with 9-[18F] fluoropropyl-（＋）-dihydrotetrabenazine （[18F]AV-133） was used before, and 15 and 90 days after the beginning of acute MPTP treatment. The imaging showed evident progressive loss of striatal uptake of [18SF]AV-133. The dopaminergic denervation severity had a significant linear correlation with the clinical rating scores and the bradykinesia subscores. These findings demonstrated that [18F]AV-133 PET imaging is a useful tool to noninvasively evaluate the evolution of monoaminergic terminal loss in a monkey model of MPTP-induced parkinsonism.

关 键 词：Parkinson＇s disease non-human primate [18F]AV-133 VMAT2 positron emission tomography 

分 类 号：R742.5[医药卫生—神经病学与精神病学]