A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.

Maria-João Ribeiro; Stéphane Thobois; Ebba Lohmann; Sophie Tezenas Du Montcel; Suzanne Lesage; Antoine Pelissolo; Bruno Dubois; Luc Mallet; Pierre Pollak; Yves Agid; Emmanuel Broussolle; Alexis Brice; Philippe Remy

doi:10.2967/jnumed.109.063529

A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.

Maria-João Ribeiro ^{1, *} Stéphane Thobois ² Ebba Lohmann ^{3, 4} Sophie Tezenas Du Montcel ^{5, 6} Suzanne Lesage ⁷ Antoine Pelissolo ⁸ Bruno Dubois ^{3, 4, 9} Luc Mallet ^{7, 10} Pierre Pollak ¹¹ Yves Agid ^{3, 12} Emmanuel Broussolle ² Alexis Brice ^{3, 13} Philippe Remy ^{14, 15}

* Auteur correspondant

1 SHFJ - Service Hospitalier Frédéric Joliot

2 Hôpital Neurologique

3 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière

4 Department of the Central Nervous System Disorders

5 Service de biostatistiques et information médicale [CHU Pitié-Salpêtrière]

6 Modelisation in Clinical Research

7 Neurologie et thérapeutique expérimentale

8 Service de psychiatrie adulte

9 Centre de référence sur les démences rares et maladie de Pick

10 Behavior, Emotion and Basal Ganglia

11 Département de neurologie

12 CIC AP-HP (pitie-Salpetriere)/inserm

13 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]

14 Service de néphrologie et transplantation

15 Hôpital Henri Mondor

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

Type de document :

Article dans une revue

Journal of Nuclear Medicine, Society of Nuclear Medicine, 2009, 50 (8), pp.1244-50. 〈10.2967/jnumed.109.063529〉

Domaine :

Sciences du Vivant [q-bio] / Neurosciences [q-bio.NC]

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00529647
Contributeur : Marc Savasta <>
Soumis le : mardi 26 octobre 2010 - 11:16:47
Dernière modification le : vendredi 31 août 2018 - 08:47:54

A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.

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A multitracer dopaminergic PET study of young-onset parkinsonian patients with and without parkin gene mutations.

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