[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration

Purpose To study the feasibility of the in vivo [ 18 F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNp...

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Published in:European journal of nuclear medicine and molecular imaging 2020-10, Vol.47 (11), p.2602-2612
Main Authors: Rodríguez-Chinchilla, Tatiana, Quiroga-Varela, Ana, Molinet-Dronda, Francisco, Belloso-Iguerategui, Arantzazu, Merino-Galan, Leyre, Jimenez-Urbieta, Haritz, Gago, Belén, Rodriguez-Oroz, María Cruz
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Cardiology
Cross-Sectional Studies
Disease Models, Animal
Imaging
Medicine
Medicine & Public Health
Microglia
Neurology
Nuclear Medicine
Oncology
Original Article
Orthopedics
Positron-Emission Tomography
Pyrazoles
Pyrimidines
Radiology
Rats
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Summary:Purpose To study the feasibility of the in vivo [ 18 F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNpc). Methods We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either hα-syn (AAV-hα-syn) or green fluorescent protein (AAV-GFP) were performed in rats ( n  = 60). In vivo [ 18 F]-DPA-714 PET imaging was performed at different time points after inoculation (p.i.) of the viral vector (24 and 72 h and 1, 2, 3, and 16 weeks). Images were analyzed to compute values of binding potential (BP) in the SNpc and striatum using a volume of interest (VOI) analysis. Immunohistochemistry of markers of dopaminergic degeneration (tyrosine hydroxylase (TH)), microglia (Iba-1), and astrocytes (GFAP) was carried out. Binding potential (BP) of [ 18 F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers. Results In the SNpc of AAV-hα-syn rats, there was higher in vivo [ 18 F]-DPA-714 BP ( p  
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-020-04772-4