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EJNMMI Research
Published in: EJNMMI Research 1/2020

Open Access 01-12-2020 | Positron Emission Tomography | Original research

[18F]FEPPA PET imaging for monitoring CD68-positive microglia/macrophage neuroinflammation in nonhuman primates

Authors: Matthew Zammit, Yunlong Tao, Miles E. Olsen, Jeanette Metzger, Scott C. Vermilyea, Kathryn Bjornson, Maxim Slesarev, Walter F. Block, Kerri Fuchs, Sean Phillips, Viktorya Bondarenko, Su-Chun Zhang, Marina E. Emborg, Bradley T. Christian

Published in: EJNMMI Research | Issue 1/2020

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Abstract

Purpose

The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [18F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA).

Methods

In vivo positron emission tomography (PET) imaging with [18F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration.

Results

Based on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [18F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = − 0.085 ± 0.018. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral putamen (p = 0.0004). [18F]FEPPA PET AI showed a positive correlation with CD68 immunoreactivity AI ratings in the monkeys (Spearman’s ρ = 0.94; p = 0.005).

Conclusion

These findings reveal that [18F]FEPPA PET is an effective marker for detecting increased CD68-positive microglial/macrophage activation and demonstrates sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.
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Metadata
Title
[18F]FEPPA PET imaging for monitoring CD68-positive microglia/macrophage neuroinflammation in nonhuman primates
Authors
Matthew Zammit
Yunlong Tao
Miles E. Olsen
Jeanette Metzger
Scott C. Vermilyea
Kathryn Bjornson
Maxim Slesarev
Walter F. Block
Kerri Fuchs
Sean Phillips
Viktorya Bondarenko
Su-Chun Zhang
Marina E. Emborg
Bradley T. Christian
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00683-5

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