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A Multitracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

Year: 2009

Type: article

Abstract: UNLABELLED: 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). CONCLUSION: Carriers of parkin mutations are indistinguishable on PET markers of dopaminergic dysfunction from other YOPD patients with long disease duration.

Source: Journal of Nuclear Medicine

DOI: 10.2967/jnumed.109.063529