References of "Lemaire, Christian"
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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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See detail18F LABELING OF BIOMOLECULES USING CLICK CHEMISTRY FOR PET APPLICATIONS : SYNTHETIC DEVELOPMENTS
Thonon, David ULg; Flagothier, Jessica ULg; Paris, Jérôme ULg et al

in Drugs of the Future (2008, August), 33(A), 235

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See detailClick chemistry for 18F labelling of bioactive compounds
Paris, Jérôme ULg; Thonon, David ULg; kech, cecile et al

Poster (2008, July 03)

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See detailCyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
Lacan, Goran; Plenevaux, Alain ULg; Rubins, Daniel J. et al

in European Journal of Nuclear Medicine and Molecular Imaging (2008), 35(12), 2256-66

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for ... [more ▼]

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. MATERIALS AND METHODS: Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. RESULTS: MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. CONCLUSIONS: These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation. [less ▲]

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See detailLes corrélats métaboliques des processus contrôlés en mémoire dans la maladie d'Alzheimer très débutante
Bastin, Christine ULg; Kerrouche, Nacer; Lekeu, Françoise ULg et al

in Ergis, Anne-Marie; Fiori, N.; Chaby, L. (Eds.) et al Xème colloque international sur le vieillissement cognitif (2008)

Les processus contrôlés et automatiques de récupération mnésique ont été évalués au moyen de la Procédure de Dissociation des Processus appliquée à une tâche de complètement de trigrammes chez 59 patients ... [more ▼]

Les processus contrôlés et automatiques de récupération mnésique ont été évalués au moyen de la Procédure de Dissociation des Processus appliquée à une tâche de complètement de trigrammes chez 59 patients diagnostiqués comme « questionable Alzheimer’s disease » (QAD ou Mild Cognitive Impairment). Par ailleurs, le métabolisme cérébral du glucose des patients a été mesuré par FDG-PET. Comparativement à des volontaires âgés sains appariés, le profil mnésique des patients QAD était caractérisé par un déficit des processus contrôlés, mais une préservation des processus automatiques. Après un suivi de 30 mois, 27 des patients ont développé une maladie d’Alzheimer, tandis que 23 patients restèrent des QAD stables (9 sujets n’ont pas complété le suivi ou ont reçu un autre diagnostic au terme de celui-ci). Les deux sous-groupes présentaient le même degré de déclin des processus de mémoire contrôlés. Des corrélations cognitivo-métaboliques, ainsi qu’une analyse en composantes principales, ont permis de montrer que les corrélats métaboliques des processus contrôlés (à l’entrée dans l’étude) n’étaient les mêmes chez les patients qui allaient développer la maladie d’Alzheimer et chez les patients qui allaient rester stables. Chez les patients qui développaient ultérieurement une maladie d’Alzheimer, l’utilisation correcte des processus contrôlés était positivement corrélée à l’activité du cortex préfrontal dorsomédian, qui pourrait jouer un rôle dans les processus réflexifs de monitoring agissant sur les produits de la récupération. L’activité du cortex préfrontal dorsomédian était corrélée à l’activité métabolique des régions frontales bilatérales et du cortex cingulaire postérieur. Par contraste, chez les patients QAD stables, nous avons trouvé une corrélation avec la formation hippocampique antérieure, une région qui intervient dans la réactivation de l’épisode d’encodage des événements. [less ▲]

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See detailPET/CT of skull base meningiomas using 2-F-18-fluoro-L-tyrosine: Initial report
Rutten, Isabelle; Cabay, Jean-Evrard ULg; Withofs, Nadia ULg et al

in Journal of Nuclear Medicine (2007), 48(5), 720-725

Precise delineation of the shape of skull base meningiomas is critical for their treatment and follow-up but is often difficult using conventional imaging such as CT and MRI. We report our results with ... [more ▼]

Precise delineation of the shape of skull base meningiomas is critical for their treatment and follow-up but is often difficult using conventional imaging such as CT and MRI. We report our results with PET/CT and 2-(18)F-fluoro-L-tyrosine ((18)F-TYR), a marker of amino acid transport, as part of the yearly follow-up of irradiated patients. METHODS: Eleven patients (mean age, 56.5 y) with skull base meningiomas (n=13 lesions) previously irradiated were included. All patients received 300 MBq of (18)F-TYR and were imaged after 30 min of uptake, using a dedicated PET/CT system. The images were first visually examined, and regions of interest (ROI) were then placed over the transaxial PET slice showing the highest uptake. Another ROI was placed over the normal parietal cortex. Tumor-to-cortex activity ratios were obtained by dividing the maximum pixel value in the tumor ROI by the maximum pixel value in the cortex ROI. The PET/CT images were compared with the MR images obtained as part of routine follow-up. RESULTS: Accumulation of the tracer was higher in all meningiomas than in the surrounding tissue. The tumor-to-cortex activity ratio was 2.53 +/- 0.35 (range, 1.3-6). Nonneoplastic tissue such as hyperemic cavernous sinus did not take up the radionuclide and was therefore easily distinguished from the meningioma. The (18)F-TYR anomalies completely overlapped with the MR image in 54% of the tumors, extended beyond the MRI lesion in 38% of the tumors, and were smaller in 8% of the tumors. CONCLUSION: Meningiomas of the skull base are clearly visualized using (18)F-TYR PET/CT, even after irradiation. In addition to MRI, (18)F-TYR PET/CT images may contribute to the evaluation, delineation, and follow-up of these tumors. [less ▲]

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See detailRadiochemical synthesis and tissue distribution of p-[F-18]DMPPF, a new 5-HT1A ligand for PET, in rats
Defraiteur, Caroline; Lemaire, Christian ULg; Luxen, André ULg et al

in Nuclear Medicine & Biology (2006), 33(5), 667-675

Several studies have demonstrated the potential of p-[F-18]MPPF as a radiophanilaceutical to study the 5-HT1A receptor family in animals and humans. A structural modification leading to a higher ... [more ▼]

Several studies have demonstrated the potential of p-[F-18]MPPF as a radiophanilaceutical to study the 5-HT1A receptor family in animals and humans. A structural modification leading to a higher radioactive signal at an equipotent dose would greatly enhance this potential. With this goal, the desmethylated 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamidolethyl]-piperazine (p-MPPF), identified as p-DMPPF, was synthesized, labeled with fluorine-18 and evaluated through ex vivo tissue distribution in rats. The new compounds p-DMPPF, p-DMPPNO2, MEM-p-MPPF and MEM-p-MPPNO2 were isolated and fully identified (H-1 and C-13 NMR, LC-MS). The final compound, p-[F-18]DMPPF, was obtained ready for injection, with an overall radiochemical yield of 10% (EOB corrected) within 90 min and a specific activity of 62 GBq/mu mol. Tissue distributions showed that the carbon-fluorine bond was stable in vivo and that this compound could cross the blood-brain barrier. For kidney, lung, heart, spleen, bone, testicle, liver and muscle, the percentage of injected dose per gram of tissue obtained with p-[F-18]DMPPF was of the same order of magnitude as that of p-[F-18]MPPF. The amount of radioactivity reaching the brain was much higher (approximately fivefold at 60 min) for p-[F-18]DMPPF compared with p-[F-18]MPPF, which was taken as reference. The distribution and specificity were in total agreement with the known localization of 5-HT1A receptors in rats. The radioactivity increase was more important for specific tissues (hippocampus and frontal cortex) than for cerebellum or striatum, leading to better contrast (hippocampus/cerebellum=5.8 at 60 min). The levels of metabolites found in plasma showed that p-[F-18]DMPPF appears to be less metabolized than p-[F-18]MPPF. p-[F-18]DMPPF deserves further evaluation as a radiopharmaceutical candidate. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

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See detailDecomposition of metabolic brain clusters in the frontal variant of frontotemporal dementia
Salmon, Eric ULg; Kerrouche, Nacer; Herholz, Karl et al

in NeuroImage (2006), 30(3), 871-878

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research ... [more ▼]

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient. [less ▲]

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See detailDEVELOPPEMENT D'INHIBITEURS SELECTIFS DE LA TRYPTOPHANE HYDROXYLASE
Giacomelli, Fabrice ULg; Luxen, André ULg; Lemaire, Christian ULg et al

Conference (2006, February 03)

Comprendre la façon dont le cerveau travaille et en particulier le mode de communication de ses cellules est un rêve que beaucoup de chercheurs caressent. A l’heure actuelle, une des rares certitudes à ... [more ▼]

Comprendre la façon dont le cerveau travaille et en particulier le mode de communication de ses cellules est un rêve que beaucoup de chercheurs caressent. A l’heure actuelle, une des rares certitudes à son sujet est qu’un de ses modes de transmission d’informations utilise des « messagers » chimiques appelés neurotransmetteurs. Parmi ceux-ci, la sérotonine (5-HT) revêt une importance particulière. En effet, la 5-HT est impliquée dans de nombreuses fonctions (apprentissage, locomotion, sommeil,…) et pathologies (dépressions, démences, schizophrénies,…). Dès lors, l'étude in vivo chez l'homme des neurones sérotoninergiques ainsi que la quantification de la vitesse de biosynthèse de la 5-HT sont des domaines d'études fondamentaux pour lesquels la tomographie à émission de positons (TEP) constitue un outil de choix. Pour mener à bien ces différentes expérimentations, deux stratégies sont envisageables : - L’emploi d'un traceur capable de suivre la chaîne métabolique du tryptophane conduisant à la 5-HT tout en évitant les autres voies métaboliques. - L’utilisation d'un inhibiteur de la TrpOH (enzyme limitant du processus). Dans le cadre de cette présentation, nous nous intéresserons plus particulièrement à la deuxième stratégie. [less ▲]

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