Publication date: Mar 23, 2020
To study the feasibility of the in vivo [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 ?-synuclein (h?-syn) in the substantia nigra pars compacta (SNpc).
We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either h?-syn (AAV-h?-syn) or green fluorescent protein (AAV-GFP) were performed in rats (n?=?60). In vivo [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 [F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers.
In the SNpc of AAV-h?-syn rats, there was higher in vivo [F]-DPA-714 BP (p?
Rodr’iguez-Chinchilla, T., Quiroga-Varela, A., Molinet-Dronda, F., Belloso-Iguerategui, A., Merino-Galan, L., Jimenez-Urbieta, H., Gago, B., and Rodriguez-Oroz, M.C. -DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration. 24452. 2020 Eur J Nucl Med Mol Imaging.