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

Abstract：

PURPOSE:To study the feasibility of the in vivo [18F]-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 [18F]-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 [18F]-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 [18F]-DPA-714 BP (p < 0.05) and increased number of post-mortem Iba-1+ cells (p < 0.05) from second week p.i. onwards, which were highly correlated (p < 0.05) between each other. These findings antedated the nigral reduction of TH+ cells that occurs since third week p.i. (p < 0.01). In addition, the [18F]-DPA-714 BP was inversely correlated (p < 0.05) with the TH+ cells. In contrast, GFAP+ cells only increased at 16 weeks p.i. and did not correlate with the in vivo results. In the striatum, no changes in the number of Iba-1+ and GFAP+ cells were observed, but an increment in the [18F]-DPA-714 BP was found at 16 weeks p.i. CONCLUSIONS:Our study showed that in vivo PET study with [18F]-DPA-714 is a selective and reliable biomarker of microglial activation and could be used to study preclinical stages of Parkinson's disease (PD) and to monitor the progression of the disease.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Rodríguez-Chinchilla T,Quiroga-Varela A,Molinet-Dronda F,Belloso-Iguerategui A,Merino-Galan L,Jimenez-Urbieta H,Gago B,Rodriguez-Oroz MC

doi

10.1007/s00259-020-04772-4

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

2602-2612

issue

eissn

1619-7070

issn

1619-7089

pii

10.1007/s00259-020-04772-4

journal_volume

pub_type

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