1Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
2Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
3Wincon Theracells Biotechnologies Inc., Nanning 530003, China
4Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875, China
5Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
6Beijing Key Laboratory on Parkinson’s Disease, Beijing 100053, China

Abstract 

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 [18F]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.

Keywords

Parkinson’s disease; non-human primate; [18F]AV-133; VMAT2; positron emission tomography

[SpringerLink]