title: A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.
abstract: 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.
authors.affiliation: CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France. maria-joao.ribeiro@cea.fr
authors.forename: Maria-João
authors.initials: MJ
authors.lastname: Ribeiro
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Sophie Tezenas
authors.initials: ST
authors.lastname: du Montcel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lesage
authors.forename: Antoine
authors.initials: A
authors.lastname: Pelissolo
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Luc
authors.initials: L
authors.lastname: Mallet
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.forename: Yves
authors.initials: Y
authors.lastname: Agid
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Philippe
authors.initials: P
authors.lastname: Remy
mesh_terms: 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*
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein