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Original research
Marina Emborg
University of Wisconsin Madison
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9351-6641
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 demonstrate sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.
Keywords
FEPPA, TSPO, CD68, microglia, macrophage, neuroinflammation, monkeys, graft
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CURRENT STATUS: Published
View the published article at EJNMMI Research.
Version 2
Posted 31 Jul, 2020
No community comments so far
Editorial decision: Accept
On 28 Jul, 2020
Reviewer #1 agreed
On 27 Jul, 2020
Review #1 received
Received 27 Jul, 2020
Editor assigned
On 27 Jul, 2020
Reviewers invited
Invitations sent on 27 Jul, 2020
Submission checks complete
On 26 Jul, 2020
Editor invited
On 26 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 23 Apr, 2020
Review #1 received
Received 30 Mar, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 22 Mar, 2020
Reviewers invited
Invitations sent on 20 Mar, 2020
Editor assigned
On 19 Mar, 2020
Editor invited
On 18 Mar, 2020
Submission checks complete
On 12 Mar, 2020
First submitted
On 11 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
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See the published version of this preprint at EJNMMI Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original research
Marina Emborg
University of Wisconsin Madison
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9351-6641
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at EJNMMI Research.
Version 2
Posted 31 Jul, 2020
No community comments so far
Editorial decision: Accept
On 28 Jul, 2020
Reviewer #1 agreed
On 27 Jul, 2020
Review #1 received
Received 27 Jul, 2020
Editor assigned
On 27 Jul, 2020
Reviewers invited
Invitations sent on 27 Jul, 2020
Submission checks complete
On 26 Jul, 2020
Editor invited
On 26 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 23 Apr, 2020
Review #1 received
Received 30 Mar, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 22 Mar, 2020
Reviewers invited
Invitations sent on 20 Mar, 2020
Editor assigned
On 19 Mar, 2020
Editor invited
On 18 Mar, 2020
Submission checks complete
On 12 Mar, 2020
First submitted
On 11 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at EJNMMI Research.
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 demonstrate sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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