A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.
The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using (18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-fluoro-l-DOPA), (11)C-PE2I, and (11)C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuropsychologic characteristics of these patients with PET results.


METHODS
A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K(i)) of (18)F-fluoro-l-DOPA and the binding potential (BP) of (11)C-PE2I (BP(DAT)) and of (11)C-raclopride (BP(D2)) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed.


RESULTS
In YOPD patients, (18)F-fluoro-l-DOPA K(i) values were reduced to 68% (caudate) and 40% (putamen) of normal values (P < 0.0001). This decrease was symmetric and comparable for nonparkin and parkin patients. No correlation was found between the K(i) values and cognitive or motor status. (11)C-PE2I BP(DAT) values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P < 0.0001) and did not differ between the 2 YOPD populations. The mean (11)C-raclopride BP(D2) values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P < 0.02) and did not differ between nonparkin and parkin patients. SPM analyses showed in patients an additional decrease of (11)C-raclopride in the frontal cortex and a decrease of (18)F-fluoro-l-DOPA and (11)C-PE2I uptake in the substantia nigra bilaterally (P < 0.05, false-discovery rate-corrected).


CONCLUSIONS
Carriers of parkin mutations are indistinguishable on PET markers of dopaminergic dysfunction from other YOPD patients with long disease duration.
Ribeiro
Maria-João
MJ
CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France. maria-joao.ribeiro@cea.fr
Thobois
Stéphane
S
Lohmann
Ebba
E
du Montcel
Sophie Tezenas
ST
Lesage
Suzanne
S
Pelissolo
Antoine
A
Dubois
Bruno
B
Mallet
Luc
L
Pollak
Pierre
P
Agid
Yves
Y
Broussolle
Emmanuel
E
Brice
Alexis
A
Remy
Philippe
P
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D011868:Radioisotopes / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000378:metabolism*; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein