Browsing by Author "Hantraye, P"

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    Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease
    (Nature Publishing Group, 2009-09) Kas, A; Bottlaender, MA; Gallezot, JD; Vidailhet, M; Villafane, G; Grégoire, MC; Coulon, CM; Valette, H; Dollé, F; Ribeiro, MJ; Hantraye, P; Remy, P
    Smoking is associated with a lower incidence of Parkinson's disease (PD), which might be related to a neuroprotective action of nicotine. Postmortem studies have shown a decrease of cerebral nicotinic acetylcholine receptors (nAChRs) in PD. In this study, we evaluated the decrease of nAChRs in PD in vivo using positron emission tomography (PET), and we explored the relationship between nAChRs density and PD severity using both clinical scores and the measurement of striatal dopaminergic function. Thirteen nondemented patients with PD underwent two PET scans, one with 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine (6-[18F]fluoro-L-DOPA) to measure the dopaminergic function and another with 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[18F]fluoro-A-85380), a radiotracer with high affinity for the nAChRs. Distribution volumes (DVs) of 2-[18F]fluoro-A-85380 measured in the PD group were compared with those obtained from six nonsmoking healthy controls, with regions-of-interest and voxel-based approaches. Both analyses showed a significant (P <0.05) decrease of 2-[18F]fluoro-A-85380 DV in the striatum (−10%) and substantia nigra (−14.9%) in PD patients. Despite the wide range of PD stages, no correlation was found between DV and the clinical and PET markers of PD severity. © 2009, Nature Publishing Group.
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    Positron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy.
    (Society for Neuroscience, 2009-02-04) Leriche, L; Bjorklund, T; Breysse, N; Besret, L; Grégoire, MC; Carlsson, T; Dollé, F; Mandel, RJ; Déglon, N; Hantraye, P; Kirik, D
    In vivo gene transfer using viral vectors is an emerging therapy for neurodegenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [11C]raclopride [(S)-(–)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) enzymes using an rAAV5 vector normalizes the increased [11C]raclopride binding in hemiparkinsonian rats. Importantly, we show in vivo by microPET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [11C]raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to follow TH + GCH1 gene therapy in PD patients and provide an additional objective measure to a potential clinical trial using rAAV vectors to deliver L-3,4-dihydroxyphenylanaline in the brain. © 2009, Society for Neuroscience
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    Radiosynthesis of 2-[6-chloro-2-(4-iodophenyl)imidazo [1,2-a]pyridin-3-yl]-N-ethyl-N-[C-11]methyl-acetamide, [C-11]CLINME, a novel radioligand for imaging the peripheral benzodiazepine receptors with PET
    (Wiley-Blackwell, 2007-03) Thominiaux, CJ; Mattner, F; Greguric, I; Boutin, H; Chauveau, F; Kuhnast, B; Grégoire, MC; Loc'h, C; Valette, H; Bottlaender, MA; Hantraye, P; Tavitian, B; Katsifis, A; Dollé, F
    Recently, a new 2-(iodophenyl)imidazo[1,2-a]pyridineacetamide series has been developed as iodine-123-labelled radioligands for imaging the peripheral benzodiazepine receptors using single photon emission tomography. Within this series, 2-[6-chloro-2-(4-iodophenyl)-imidazo[1,2-alpyridin-3-yl]-N-ethyl-N-methyl-acetamide (CLINME) was considered as an appropriate candidate for positron emission tomography imaging and was isotopically labelled with carbon-11 (T-1/2: 20.38 min) at the methylacetamide side chain from the corresponding nor-analogue using [C-11]methyl iodide and the following experimental conditions: (1) trapping at -10 degrees C of [C-11]methyl iodide in a 1/2 (v:v) mixture of DMSO/DMF (300 mu l) containing 0.7-1.0 mg of the precursor for labelling and 3-5 mg of powdered potassium hydroxide (excess); (2) heating the reaction mixture at 110 degrees C for 3 min under a nitrogen stream; (3) diluting the residue with 0.6 ml of the HPLC mobile phase; and (4) purification using semi-preparative HPLC (Zorbax(R) SB18, Hewlett Packard, 250 x 9.4 mm). Typically, starting from a 1.5Ci (55.5 GBq) [C-11]CO2 production batch, 120-150 mCi (4.44-5.55 GBq) of [C-11]CLINME were obtained (16-23% decay-corrected radiochemical yield, n = 12) within a total synthesis time of 24-27 min (Sep-pak(R)Plus-based formulation included). Specific radio-activities ranged from 0.9 to 2.7 Ci/mu mol (33.3-99.9 GBq/mu mol) at the end of radiosynthesis. © 2007, Wiley-Blackwell.
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    Segmentation of small animal PET/CT mouse brain scans using an MRI-based 3D digital atlas: application in a neuroinflammation mouse model.
    (Institute of Electrical and Electronics Engineers (IEEE), 2010-09-02) Delzescaux, T; Lebenberg, J; Raguet, H; Hantraye, P; Souedet, N; Grégoire, MC
    The work reported in this paper aimed at developing and testing an automated method to calculate the biodistribution of a specific PET tracer in mouse brain PET/CT images using an MRI-based 3D digital atlas. Surface-based registration strategy and affine transformation estimation were considered. Such an approach allowed overcoming the lack of anatomical information in the inner regions of PET/CT brain scans. Promising results were obtained in one mouse (on two scans) and will be extended to a neuroinflammation mouse model to characterize the pathology and its evolution. Major improvements are expected regarding automation, time computation, robustness and reproducibility of mouse brain segmentation. Due to its generic implementation, this method could be successfully applied to PET/CT brain scans of other species (rat, primate) for which 3D digital atlases are available. © 2011 IEEE