Abstract
Purpose The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [ 18 F]FEPPA has the sensitivity for detecting changes in microglial 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 [ 18 F]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 visual inspection of the imaging data and assessment of radiotracer uptake, nonhuman primates with allogeneic grafts showed increased [ 18 F]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 = -0.110 ± 0.025. 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 nucleus (p = 0.0004). [ 18 F]FEPPA PET standard uptake values normalized to the contralateral putamen (SUV norm ) showed a positive correlation with CD68 immunoreactivity ratings in the monkeys (Pearson’s r = 0.83; p = 0.0008). Conclusion These findings reveal that [ 18 F]FEPPA PET is an effective marker for detecting increased microglial activation and demonstrate sufficient sensitivity to detect small changes in neuroinflammation in vivo following allogeneic cell engraftment.
PET imaging of dopamine receptors and transporters in neuropsychiatric disoders and phramcological studies.