PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease.
Human retinal pigment epithelial (hRPE) cells produce L-dopa, are easily harvested and expanded in culture, and, attached to microcarriers, can survive in the brain without immunosuppression. Studies in rats, primates, and parkinsonian patients have demonstrated that striatally implanted hRPE cells attached to gelatin microcarriers (RPE-GM) are able to improve parkinsonian symptoms and are well tolerated for extended periods. In moderately to severely impaired monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced parkinsonism receiving a unilateral RPE-GM implant in the putamen, there was a 39% improvement in clinical scores over the first 2 months post-implant. Positron emission tomography (PET) with [18F]fluoro-L-dopa (FDOPA) showed increased accumulation in the implanted putamen and a concomitant decrease in [11C]raclopride binding in the same area, suggesting increased dopamine release compared to the contralateral putamen. We report the first in vivo visualization of hRPE cells and their effects, implicating a dopaminergic mechanism of action.
Doudet
D J
DJ
Pacific Parkinson Research Centre, Department of Medicine/Neurology, University of British Columbia, Vancouver, BC, Canada V6T 2B5. ddoudet@interchange.ubc.ca
Cornfeldt
M L
ML
Honey
C R
CR
Schweikert
A W
AW
Allen
R C
RC
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000628:therapy*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery*; D020891:Raclopride / Q000378:metabolism; D011869:Radioligand Assay; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C043437:fluorodopa F 18; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D004298:Dopamine