Browsing by Author "Dolle, F"
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- ItemCerebral monoamine oxidase a inhibition in tobacco smokers confirmed with PET and [c-11]befloxatone(Lippincott, Williams & Wilkins, 2009-02) Leroy, C; Bragulat, V; Berlin, I; Grégoire, MC; Bottlaender, MA; Roumenov, D; Dolle, F; Bourgeois, S; Penttilae, J; Artiges, E; Martinot, JL; Trichard, CThe inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [11C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [11C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco. © 2009, Lippincott, Williams & Wilkins
- ItemDecrease 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; Dolle, F; Ribeiro, MJ; Hantraye, P; Remy, PSmoking 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.
- ItemIn vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors(John Wiley and Sons, 2007-08-06) Boutin, H; Chauveau, F; Thominiaux, C; Kuhnast, B; Grégoire, MC; Jan, S; Trebossen, R; Dolle, F; Tavitian, B; Mattner, F; Katsifis, AThe peripheral benzodiazepine receptor (PBR) is expressed by microglial cells in many neuropathologies involving neuroinflammation. PK11195, the reference compound for PBR, is used for positron emission tomography (PET) imaging but has a limited capacity to quantify PBR expression. Here we describe the new PBR ligand CLINME as an alternative to PK11195. In vitro and in vivo imaging properties of [11C]CLINME were studied in a rat model of local acute neuroinflammation, and compared with the reference compound [11C]PK11195, using autoradiography and PET imaging. Immunohistochemistry study was performed to validate the imaging data. [11C]CLINME exhibited a higher contrast between the PBR-expressing lesion site and the intact side of the same rat brain than [11C]PK11195 (2.14 ± 0.09 vs. 1.62 ± 0.05 fold increase, respectively). The difference was due to a lower uptake for [11C]CLINME than for [11C]PK11195 in the non-inflammatory part of the brain in which PBR was not expressed, while uptake levels in the lesion were similar for both tracers. Tracer localization correlated well with that of activated microglial cells, demonstrated by immunohistochemistry and PBR expression detected by autoradiography. Modeling using the simplified tissue reference model showed that R1 was similar for both ligands (R1 ∼ 1), with [11C]CLINME exhibiting a higher binding potential than [11C]PK11195 (1.07 ± 0.30 vs. 0.66 ± 0.15). The results show that [11C]CLINME performs better than [11C]PK11195 in this model. Further studies of this new compound should be carried out to better define its capacity to overcome the limitations of [11C]PK11195 for PBR PET imaging. © 2007 Wiley-Liss, Inc.
- ItemIn vivo imaging of neuroinflammation: a comparative study between [F-18]PBR111, [C-11]CLINME and [C-11]PK11195 in an acute rodent model(Springer, 2010-05-01) van Camp, N; Boisgard, R; Kuhnast, B; Thézé, B; Viel, T; Grégoire, MC; Chauveau, F; Boutin, H; Katsifis, A; Dolle, F; Tavitian, BThe key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [F-18]PBR111 in a rodent model of acute inflammation and compare it with [C-11]CLINME, an C-11-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [C-11]PK11195. We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [F-18]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [F-18]PBR111 administration, induces a rapid and complete displacement of [F-18]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [C-11]PK11195. [F-18]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of F-18 over C-11, these results support [F-18]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging. © 2010, Springer.