References of "Lemaire, Christian"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailTIME-DEPENDENT PREFERENTIAL IN VIVO D2 OCCUPANCY BY AMISULPRIDE IN THE MEDIAL STRIATUM – CONTINUOUS MEASUREMENT USING A BETA MICROPROBE SYSTEM
Warnock, Geoffrey ULg; Goblet, David ULg; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 105

Detailed reference viewed: 28 (7 ULg)
Full Text
Peer Reviewed
See detailUSE OF A BETA MICROPROBE SYSTEM AS AN AFFORDABLE TRANSLATIONAL TOOL COMPARED TO PET – EXAMPLES USING FDG AND 18F-FALLYPRIDE BINDING
Warnock, Geoffrey ULg; Goblet, David ULg; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 55

Detailed reference viewed: 37 (9 ULg)
Full Text
Peer Reviewed
See detailTHE USEFULNESS OF AN ARTERIOVENOUS SHUNT COMBINED WITH A BETA MICROPROBE FOR THE MEASUREMENT OF INPUT FUNCTION IN RATS
Warnock, Geoffrey ULg; Goblet, David ULg; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 106

Detailed reference viewed: 30 (13 ULg)
Full Text
Peer Reviewed
See detailModified Non-Ionic Solid Supports: a Way to High Activity Fluorine-18 Radiochemistry in Microfluidic Devices
Aerts, Joël ULg; Voccia, Samuel; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 12

Detailed reference viewed: 35 (6 ULg)
Full Text
Peer Reviewed
See detailTertiary Alcohols to Avoid Evaporation in Fluorine-18 Labeling
Aerts, Joël ULg; Voccia, Samuel; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 204

Detailed reference viewed: 47 (8 ULg)
Full Text
Peer Reviewed
See detailNew Improvements in the Enantioselective Synthesis of 2-[18F]Fluoro-L-Tyrosine and 6-[18F]Fluoro-L-Dopa
Libert, Lionel ULg; Lemaire, Christian ULg; Denoël, Thibaut ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 196

Detailed reference viewed: 51 (14 ULg)
Full Text
Peer Reviewed
See detailLarge Scale Preparation of [18]Fluoromethoxybenzyl Bromides, Key Precursors for 2-[18F]Fluoro-L-Tyrosine and 6-[18F]Fluoro-L-Dopa
Libert, Lionel ULg; Lemaire, Christian ULg; Wouters, Ludovic ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 292

Detailed reference viewed: 66 (9 ULg)
Full Text
Peer Reviewed
See detailAre Ionic Liquid Useful for Fluorine-18 Labeling?
Aerts, Joël ULg; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 193

Detailed reference viewed: 40 (6 ULg)
Full Text
Peer Reviewed
See detailUse of Organic Bases for 18F-Fluoride Anion Exchange Elution avoiding the Classical Azeotropic drying Step Before Labeling
Lemaire, Christian ULg; Aerts, Joël ULg; Voccia, Samuel et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 198

Detailed reference viewed: 56 (4 ULg)
Full Text
Peer Reviewed
See detailFast and Reliable Method for the Preparation of Various [18F]Fluorobenzyl Halides
Lemaire, Christian ULg; Libert, Lionel ULg; Plenevaux, Alain ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 178

Detailed reference viewed: 23 (7 ULg)
Full Text
Peer Reviewed
See detailPEPTIDE CLICK LABELLING WITH 1-(AZIDOMETHYL)-4-[18F]-FLUOROBENZENE AND REFERENCE COMPOUNDS SYNTHESIS ON SOLID SUPPORT
Thonon, David ULg; Paris, Jérôme ULg; Kech, Cecile et al

in Journal of Labelled Compounds and Radiopharmaceuticals (2009, July)

Detailed reference viewed: 32 (5 ULg)
Full Text
Peer Reviewed
See detailUniversal solid support synthesis of modified oligonucleotides labeled by click chemistry for PET studies
Flagothier, Jessica ULg; Mercier, Frederic; Kaisin, Geoffroy ULg et al

Poster (2009, May 29)

Introduction: Positron emission tomography (PET) is a high-resolution, sensitive, molecular and functional imaging technique that permits repeated, non invasive assessment and quantification of specific ... [more ▼]

Introduction: Positron emission tomography (PET) is a high-resolution, sensitive, molecular and functional imaging technique that permits repeated, non invasive assessment and quantification of specific biological and pharmacological processes in humans[1]. In regard to its physical and nuclear characteristics, fluorine-18 appears often as the radionuclide of choice for the preparation of short-lived positron-emitter radiotracers[2]. F-18 labelling reaction of biomolecules such as peptides[3], oligosaccharides, and oligonucleotides[4] (ONs) requires very mild reaction conditions. The method of choice for a highly efficient fluorine-18-labelling of ONs is today the conjugation of a prosthetic group, carrying the radioisotope, with a reactive function of the ONs. Methods: For the ligation reaction of the prosthetic group with the ONs, we selected click reaction and more particularly the CuI catalyzed formation of 1,2,3-triazole using Huisgen 1,3-dipolar cycloaddition of terminal alkynes with azides. This reaction is highly regioselective leading to 1,4-disubstituted 1,2,3-triazoles and can be performed in different solvents with very high yield[5-7]. Conjugations with ONs are usually performed at 3’-ends using a well chosen linker in order to limit degradation by exonucleases[8]. Here we report the synthesis of an alkyne-bearing linker which can be attached at 3’-ends to any sequence of ONs. Results: The linker was prepared in two steps by reaction of commercially available (R)-(+)--hydroxy--butyrolactone with propargylamine followed by protection of the primary hydroxyl with the 4,4’-dimethoxytrityl group[9]. The second step is the reaction with succinic anhydride to obtain a carboxylic function which can be attached to the Amino-SynBase CPG. The resin load was 80 µmol/g. Conclusions: We have prepared a new universal linker which allows introducing an alkyne function at the 3’-end of ONs. This alkyne modified ONs can then react under click conditions with an azide function of a prosthetic group carrying the fluorine radioisotope. As prosthetic group, we selected the 1-azido-4-(3-[18F]fluoropropoxy)benzene which is fully automated produce in our lab[10]. The further results of radiosynthesis of this prosthetic group and the results of click reactions will be presented. Acknowledgement: The authors wish to thank Teller N. from Eurogentec (Seraing, Belgium) for oligonucleotide synthesis. The authors wish to acknowledge the financial support from the Oligopet Projet of the Walloon Region. [less ▲]

Detailed reference viewed: 49 (4 ULg)
Full Text
Peer Reviewed
See detailNew Strategy for the Preparation of Clickable Peptides and Labeling with 1-(Azidomethyl)-4-[18F]-fluorobenzene for PET
Thonon, David ULg; Paris, Jérôme ULg; Kech, Cecile et al

in Bioconjugate Chemistry (2009), 20(4), 817-823

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides ... [more ▼]

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides has been developed and has also permitted the straightforward preparation of reference compounds. A complementary azide labeling agent (1-(azidomethyl)-4-[18F]-fluorobenzene) has been produced in a four step procedure in 75 min with a 34% radiochemical yield (decay corrected). Conjugation of [18F]fluoroazide with a model alkyne-neuropeptide produced the desired 18F-radiolabeled peptide in less than 15 min with a yield of 90% and excellent radiochemical purity [less ▲]

Detailed reference viewed: 28 (8 ULg)
Peer Reviewed
See detailClick chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging
Kaisin, Geoffroy ULg; Flagothier, Jessica ULg; Mercier, Frédéric et al

Poster (2009, March 18)

Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their ... [more ▼]

Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to image and quantify such biological processes. The challenge for the radiochemist is to introduce this short half-life isotope (t1/2(18F)=109.7 min) onto oligonucleotides or, more generally, biomolecules. The most common technique requires the coupling of a prosthetic group bearing the radiotracer with the biomolecule. Current methods for labeling ONs with fluorine-18 have sub-optimal yields and require a long synthesis time.{Vries2003} Click chemistry, e.g. 1,3-dipolar Huisgen cycloaddition of azides to alkynes, could be an efficient way to increase yields and reduce synthesis time (see Figure 1). This family of reactions are well suited to the radiolabelling of ONs as they are tolerant to a wide range of solvent and require mild reaction conditions and simple purifications.{Glaser2007} The major strength of this approach is its versatility: it can be easily transposed to any other kind of biomolecules (e.g. peptides, lipids) as long as they can bear an azido or alkyne moiety. Conjugations with ONs are usually performed at 3’-ends using a well-chosen linker in order to limit degradation by exonucleases and to avoid alteration of hybridization properties and siRNA gene silencing efficiency.{Kurreck2009} This also allows the development of universal solid support because synthesis occurs from the 3’ to 5’-end. The linker must fulfil a number of requirements:{Gait2001} - Bearing one alkyne, one primary and one secondary alcohol moiety; - Having a well-defined and known stereochemistry. According to these terms, we propose three different potential linkers (see Figure 2) that can be incorporated into the solid-phase synthesis of ONs. Starting materials are commercially available as pure enantiomers at an affordable price. Here we report the synthesis and characterisation of an alkyne-bearing linker and the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]-fluorobenzene). [less ▲]

Detailed reference viewed: 58 (11 ULg)
Full Text
See detailSynthesis of an universal linker to label oligonucleotides via Click Chemistry
Flagothier, Jessica ULg; Mercier, Frederic; Kaisin, Geoffroy ULg et al

Poster (2009, January 21)

For more than 3 decades, oligonucleotides have been used for therapies, imaging and diagnostics. They are known to hybridize specifically with RNA of a complementary sequence on tissue sections and more ... [more ▼]

For more than 3 decades, oligonucleotides have been used for therapies, imaging and diagnostics. They are known to hybridize specifically with RNA of a complementary sequence on tissue sections and more recently to block the expression of target mRNA when administered in vivo (1). Positron emission Tomography (PET) is a sensitive and non invasive imaging technique, and is the most advanced technology currently available for studying in vivo molecular interactions and therapeutic agents. It is a method of choice to assess the pharmacokinetics of new therapeutics agents such as modified oligonucleotides. Among positron-emitting nuclides, fluorine-18 (t1/2 = 109.8 min) appears to be the best candidate due to its favourable physical and nuclear properties. Several of the methods described in the literature to label oligonucleotides present a number of disadvantages (time of synthesis, low overall radiolabelling yield, non-universal). Due to the speed, selectiveness and the relatively mild experimentals conditions, “Click” chemistry seems a powerful technique. The most explored Click reaction is Huisgen 1,3 dipolar cycloaddition. In our case, this reaction occurs between an alkyne group presents on the oligonucleotide and an azide group on the 18F labelled prosthetic group. The originality of our strategy is the use of a universal linker diverted from the trans-4-hydroxy-proline directly connected to the oligonucleotide. This linker mimics a sugar of the oligonucleotide sequence and should improve their resistance to exonucleases. Synthesis of this compound will be presented. [less ▲]

Detailed reference viewed: 76 (3 ULg)
Peer Reviewed
See detailMultivariate analysis of cognitive profiles in Alzheimer's disease
Bastin, Christine ULg; Leclercq, Yves ULg; Collette, Fabienne ULg et al

in Proceedings of the 8th bi-annual Meeting of the Belgian Society for Neuroscience (2009)

The neuropsychological profiles of patients with early Alzheimer’s disease (AD) appear to be heterogeneous. In this study, we examined whether this heterogeneity corresponds to the existence of ... [more ▼]

The neuropsychological profiles of patients with early Alzheimer’s disease (AD) appear to be heterogeneous. In this study, we examined whether this heterogeneity corresponds to the existence of cognitively distinct subtypes of AD or rather to impairments along a continuum of performances in different cognitive domains. A large group of 187 AD patients recruited in the European project NEST-DD performed a neuropsychological battery. A factor analysis of cognitive performance identified three factors, which respectively reflected attentional/instrumental function, declarative memory and executive function. Three clustering methods were applied on the factor scores in order to explore the existence of separate groups. The clustering methods indicated that cognitive profiles among the patients were sufficiently variable to identify clusters, but there was continuity between clusters rather than clear-cut subtypes. Moreover, clusters corresponded to various combinations of relatively impaired and preserved functions, suggesting multidimensional distribution within a large population of patients. Finally, clusters of cognitive profiles were characterized by different levels of metabolism in brain regions commonly (but variably) involved or relatively preserved in AD. [less ▲]

Detailed reference viewed: 54 (0 ULg)
Full Text
Peer Reviewed
See detailCombiner les mesures métaboliques cérébrales et neuropsychologiques permet une meilleure prédiction de la conversion vers une maladie d’Alzheimer chez les patients MCI
Bastin, Christine ULg; Adam, Stéphane ULg; LEKEU, Françoise ULg et al

in Revue Neurologique (2009), 165

Introduction. Une voie de recherche neurologique importante concerne la capacité de prédire sur base de l’évaluation initiale des patients avec Mild Cognitive Impairment (MCI) ceux qui vont développer une ... [more ▼]

Introduction. Une voie de recherche neurologique importante concerne la capacité de prédire sur base de l’évaluation initiale des patients avec Mild Cognitive Impairment (MCI) ceux qui vont développer une maladie d’Alzheimer (MA). Parmi les tests neuropsychologiques, le rappel indicé avec indiçage congruent lors de l’encodage et du rappel (RI48) apparaît comme le meilleur prédicteur du devenir des patients MCI (Ivanoiu et al., 2005). D’autre part, on a montré que les mesures métaboliques cérébrales (TEP-FDG), plus particulièrement l’hypométabolisme du cortex temporopariétal, prédit le déclin cognitif global dans le MCI mieux que des mesures neuropsychologiques (Chételat et al., 2005). Le but de notre étude était d’évaluer le pouvoir de prédiction pour la conversion du MCI vers une MA de deux prédicteurs robustes (performance au RI48 et métabolisme cérébral) pris soit isolément soit ensemble. Méthode. 50 patients MCI ont subi un examen en TEP-FDG au repos et ont réalisé le test de rappel indicé RI48 et le MMSE. Au terme d’un suivi neuropsychologique de 36 mois, 28 patients ont évolué vers une MA et 22 sont restés stables. Le métabolisme cérébral et les performances cognitives ont été comparés entre « convertisseurs » et MCI-stables. Des analyses discriminantes ont ensuite permis d’évaluer la capacité de classification de l’âge, du MMSE et des mesures métaboliques et mnésiques considérés individuellement ou selon diverses combinaisons. Résultat. Par comparaison avec les MCI-stables, les « convertisseurs » montraient un hypométabolisme du cortex temporal moyen bilatéralement, du cortex pariétal inférieur droit et du précuneus droit, et de plus faibles performances initiales au RI48. Prises individuellement, les différentes mesures permettaient le même taux de classification correcte (métabolisme cérébral = 76%, RI48 = 76%). L’âge et le MMSE étaient de faibles prédicteurs (exactitude de classification = 62% et 66% respectivement). Par contre, la combinaison des mesures métaboliques et des scores au RI48 prédisaient le mieux la progression vers la MA (88%). Conclusion. Les résultats suggèrent que la stratégie optimale pour identifier quels patients MCI ont plus de risque de développer une MA est de combiner les mesures métaboliques cérébrales et la performance à un test de mémoire très sensible. [less ▲]

Detailed reference viewed: 101 (8 ULg)
Full Text
Peer Reviewed
See detailOn the multivariate nature of brain metabolic impairment in Alzheimer’s disease
Salmon, Eric ULg; Kerrouche, Nacer; Perani, Daniela et al

in Neurobiology of Aging (2009), 30

We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38 ... [more ▼]

We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38% of the total variance in a large sample of FDG-PET images obtained in 225 AD patients. One functional ensemble (PC2) included limbic structures from Papez's circuit (medial temporal regions, posterior and anterior cingulate cortex, thalamus); its disruption in AD patients was related to episodic memory impairment. Another principal component (PC1) illustrated major metabolic variance in posterior cerebral cortices, and patients' scores were correlated to instrumental functions (language and visuospatial abilities). PC3 comprised frontal, parietal, temporal and posteromedial (posterior cingulate and precuneus) cortices, and patients' scores were related to executive dysfunction and global cognitive impairment. The three main metabolic covariance networks converged in the posterior cingulate area that showed complex relationships with medial temporal structures within each PC. Individual AD scores were distributed as a continuum along PC axes: an individual combination of scores would determine specific clinical symptoms in each patient. [less ▲]

Detailed reference viewed: 169 (21 ULg)
Full Text
Peer Reviewed
See detailMetabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats
Aerts, Joël ULg; Plenevaux, Alain ULg; Lemaire, Christian ULg et al

in BMC Medical Physics (2008), 8

Background: Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among ... [more ▼]

Background: Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas. Methods: No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant. Results: The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, nocarrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions. Conclusion: This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma. [less ▲]

Detailed reference viewed: 50 (18 ULg)