[18F]FEPPA Pet Imaging for Monitoring CD68 Positive Microglia/Macrophage Neuroinflammation in Nonhuman Primates
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.
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Posted 31 Jul, 2020
On 06 Aug, 2020
On 28 Jul, 2020
On 27 Jul, 2020
Received 27 Jul, 2020
On 27 Jul, 2020
Invitations sent on 27 Jul, 2020
On 26 Jul, 2020
On 26 Jul, 2020
On 23 Apr, 2020
Received 30 Mar, 2020
On 26 Mar, 2020
On 22 Mar, 2020
Invitations sent on 20 Mar, 2020
On 19 Mar, 2020
On 18 Mar, 2020
On 12 Mar, 2020
On 11 Mar, 2020
[18F]FEPPA Pet Imaging for Monitoring CD68 Positive Microglia/Macrophage Neuroinflammation in Nonhuman Primates
Posted 31 Jul, 2020
On 06 Aug, 2020
On 28 Jul, 2020
On 27 Jul, 2020
Received 27 Jul, 2020
On 27 Jul, 2020
Invitations sent on 27 Jul, 2020
On 26 Jul, 2020
On 26 Jul, 2020
On 23 Apr, 2020
Received 30 Mar, 2020
On 26 Mar, 2020
On 22 Mar, 2020
Invitations sent on 20 Mar, 2020
On 19 Mar, 2020
On 18 Mar, 2020
On 12 Mar, 2020
On 11 Mar, 2020
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