References of "Comar, Dominique"
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See detailTissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.
Plenevaux, Alain ULg; Weissmann, D.; Aerts, Joël ULg et al

in Journal of Neurochemistry (2000), 75(2), 803-11

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving ... [more ▼]

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain. [less ▲]

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See detailSolid phase extraction : An alternative to the use of rotary evaporators for solvent removal in the rapid formulation of PET radiopharmaceuticals
Lemaire, Christian ULg; Plenevaux, Alain ULg; Aerts, Joël ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (1999), 42(1), 63-75

Solid phase extraction (SPE) was used for the formulation of several radiopharmaceuticals. The method involves dilution of the previously purified HPLC compound with water, trapping of the activity on an ... [more ▼]

Solid phase extraction (SPE) was used for the formulation of several radiopharmaceuticals. The method involves dilution of the previously purified HPLC compound with water, trapping of the activity on an SPE bed, washing off the support, elution of the radiopharmaceutical with a small volume of ethanol (<1 mL) and dilution with sterile isotonic saline solution. Recovery of the radiopharmaceuticals was always higher than 97%. Two different methods of automation were developed for the formulation of [11C] and [18F]radiopharmaceuticals. In all cases, organic solvent levels in the injectable solution were below the recommended limits. This fast (3-6 min.) and easy to automate process can be considered as an alternative to the conventional methods (rotary evaporators). Copyright © 1999 John Wiley [less ▲]

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See detailHigh-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635.
Le Bars, Didier; Lemaire, Christian ULg; Ginovart, N. et al

in Nuclear Medicine & Biology (1998), 25(4), 343-50

No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the ... [more ▼]

No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis. Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand. [less ▲]

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See detailNo-carrier-added asymmetric synthesis of alpha-methyl-alpha-amino acids labelled with fluorine-18
Damhaut, Philippe; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

in Tetrahedron (1997), 53(16), 5785-5796

Various [18F]fluoro aromatic α-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity (ee > 97%). These new radiopharmaceuticals for Positron Emission Tomography (PET), potential ... [more ▼]

Various [18F]fluoro aromatic α-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity (ee > 97%). These new radiopharmaceuticals for Positron Emission Tomography (PET), potential inhibitors of enzymatic functions, were regiospecifically labelled by nucleophilic substitution on trimethylammoniumbenzaldehyde triflate precursors 9. The [18F]fluoro aromatic aldehydes 12 obtained were easily converted to the corresponding [18F]fluorobenzyl halides [13 (X = 1)]. After alkylation of the lithium enolate of (2S,5S)-l-tert-Boc-2-tert-butyl-3,5-dimethyl-imidazolidin-4-one 2, the adducts were cleaved to give, after HPLC purification, various [18F]fluoro-α-methyl amino acid analogs with radiochemical yields of 10% (End of Bombardment, EOB) after a synthesis time of 120 min. The corresponding [19F]fluorinated amino acids 4 and [19F]fluoro intermediates were also prepared. [less ▲]

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See detailEnantioselective syntheses of no-carrier-added (nca) (S)-4-chloro-2 F-18 fluorophenylalanine and (S)-(alpha-methyl)-4-chloro-2 F-18 fluorophenylalanine
Al-Darwich, M. J.; Plenevaux, Alain ULg; Lemaire, Christian ULg et al

in Journal of Fluorine Chemistry (1996), 80(2), 117-124

(S)-4-Chloro-2-fluorophenylalanine and (S)-( a-methyl)-4-chloro-2-fluorophenylalanine were synthesized and labeled with no carrier added (n.c.a.) fluorine-18 through a radiochemical synthesis relying on ... [more ▼]

(S)-4-Chloro-2-fluorophenylalanine and (S)-( a-methyl)-4-chloro-2-fluorophenylalanine were synthesized and labeled with no carrier added (n.c.a.) fluorine-18 through a radiochemical synthesis relying on the highly enantioselective reaction between 4-chloro-2-[18F] fluorobenzyl iodide and the lithium enolate of (2s) -1-( tert-butyloxycarbonyl) -2-( tert-butyl)-3-methyl- 1,3-imidazolidine-4-one for (S) -4-chloro-2- [18F] fluorophenylalanine and (2S,5S)-1-( tert-butyloxycarbonyl) -2-( tert-butyl) -3,5-dimethyl- 1,3-imidazolidine-4-one for (S) -( a-methyl) -4-chloro-2- [18F] fluorophenylalanine. Quantities of about 20-25 mCi were obtained at the end of synthesis, ready for injection after hydrolysis and high performance liquid chromatography (HPLC) purification, with a radiochemical yield of 17%-20% corrected to the end of bombardment after a total synthesis time of 90-105 min from [18F] fluoride. The enantiomeric excesses were shown to be 97% or more for both molecules without chiral separation and the radiochemical and chemical purities were 98% or better. [less ▲]

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See detailFast Routine Production of L-[11C-methyl]methionine with Al2O3KF
Schmitz, Frédéric; Plenevaux, Alain ULg; Del-Fiore, Guy et al

in Applied Radiation & Isotopes (1995), 46(9), 893-897

No-carrier-added (nca) L-[11C-methyl]methionine was prepared via the very fast S-alkylation of L-homocysteine adsorbed on AI203/KF with [11C]iodomethane at room temperature in ethanol. The alkylation was ... [more ▼]

No-carrier-added (nca) L-[11C-methyl]methionine was prepared via the very fast S-alkylation of L-homocysteine adsorbed on AI203/KF with [11C]iodomethane at room temperature in ethanol. The alkylation was realized with a radiochemical yield of 94 +/- 4% EOB (n = 20). More than 90% (n = 20) of the precursor L-homocysteine remained adsorbed on the solid support and was eliminated by a simple filtration. After reaction, neither racemization nor by-product were detected. The purification process was thus limited to a C18 Sep-Pak followed by an alumina Sep-Pak. The radiochemical purity measured on the final solution was shown to be > 99%. The only chemical contaminant was L-homocysteine (+ 10 µg). With this new technique, L-[11C-methyl]methionine was ready for injection within 10 min from [11C]CO2 with a specific activity ranging around 37 + 5.6 GBq (1 +/- 0.15 Ci)//tmol EOB. Through this procedure L-[11C-methyl]methionine can be prepared without preparative HPLC purification, This is an important simplification for the fast routine production of one of the most widely used radiopharmaceutical compounds for PET. [less ▲]

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See detailSerotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.
Sadzot, Bernard ULg; Lemaire, Christian ULg; Maquet, Pierre ULg et al

in Journal of Cerebral Blood Flow & Metabolism (1995), 15(5), 787-97

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the ... [more ▼]

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans. [less ▲]

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See detailENANTIOSELECTIVE SYNTHESES OF NCA (S)-L-[BETA-C-11]-4-CHLOROPHENYLALANINE AND (S)-L-(ALPHA-METHYL)-[BETA-C-11]-4-CHLOROPHENYLALANINE
Plenevaux, Alain ULg; Al-Darwich, M. J.; Lemaire, Christian ULg et al

in Applied Radiation & Isotopes (1994), 45(3), 361-369

The radiolabeling of (S)-L-4-chlorophenylalanine and (S)-L-(alpha-methyl)-4-chlorophenylalanine were realized with carbon-11 at position beta through a radiochemical synthesis relying on the highly ... [more ▼]

The radiolabeling of (S)-L-4-chlorophenylalanine and (S)-L-(alpha-methyl)-4-chlorophenylalanine were realized with carbon-11 at position beta through a radiochemical synthesis relying on the highly enantioselective reaction between 4-chloro[alpha-C-11]benzyl bromide and the lithium enolate of (S)-1-(t-butyloxycarbonyl)-2-(t-butyl)-3-methyl-1,3-imidazolidine-4-one for (S)-L-[beta-C-11]-4-chlorophenylalanine and of (2S,5S)-1-(t-butyloxycarbonyl)-2-(t-butyl)-3,5-dimethyl-1,3-imidazolidin e-4-one for (S)-L-(alpha-methyl)-[beta-C-11]-4-chlorophenylalanine. Quantities of about 25-35 mCi were obtained at the end of synthesis, ready for injection, after hydrolysis and HPLC purification with a radiochemical yield of 19% corrected to EOB within 45 min. The enantiomeric excesses were shown to be greater than or equal to 97% for both molecules without chiral separation. The radiochemical and the chemical purities of the final compounds were greater than or equal to 98% and the specific activity at the end of synthesis ranged between 250-800 mCi/mu mol. [less ▲]

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See detailENANTIOSELECTIVE SYNTHESIS OF NCA (S)-L-([ALPHA-C-11]METHYL)-TRYPTOPHAN
Plenevaux, Alain ULg; Lemaire, Christian ULg; Delfiore, Guy et al

in Applied Radiation & Isotopes (1994), 45(6), 651-653

N.c.a. (S)-L-([alpha-C-11]methyl)-tryptophan was prepared by treatment at -78-degrees-C of (2S,3aR,8aS)-1,2-bis(-methoxycarbonyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2, 3-b]-indole with lithium ... [more ▼]

N.c.a. (S)-L-([alpha-C-11]methyl)-tryptophan was prepared by treatment at -78-degrees-C of (2S,3aR,8aS)-1,2-bis(-methoxycarbonyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2, 3-b]-indole with lithium diisopropylamide and [C-11]CH3I. After hydrolysis with HI and HPLC purification, the title compound was isolated with a radiochemical yield of 36% (EOB corrected) within 22 min; e.e. was shown > 97% (n = 20); specific activity was ranging between 0.8 and 1.2 Ci (30-45 GBq)/mu mol EOB. [less ▲]

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See detailEnantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride.
Lemaire, Christian ULg; Damhaut, Philippe; Plenevaux, Alain ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (1994), 35(12), 1996-2002

METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride ... [more ▼]

METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride produced by the 18O(p,n)18F nuclear reaction on enriched 18O-water led to the corresponding no-carrier-added [18F]fluoroveratraldehyde (45 +/- 5% EOB). Diiodosilane was used to prepare the corresponding [18F]fluorobenzyl iodide (36.5 +/- 5.3% EOB). Akylation of (S)-1-tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[18F]fluoro-L-dopa ready for human injection, in a 23% +/- 6% decay-corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Ci/mumole respectively. CONCLUSION: Through this procedure, starting from 250 mCi of 18F-fluoride, multimillicurie amounts (32 +/- 8.5 mCi) of no-carrier-added 6-[18F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%). [less ▲]

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See detailNUCLEOPHILIC ENANTIOSELECTIVE SYNTHESIS OF 6-[F-18]FLUORO-L-DOPA VIA 2 CHIRAL AUXILIARIES
Lemaire, Christian ULg; Plenevaux, Alain ULg; Cantineau, Robert et al

in Applied Radiation & Isotopes (1993), 44(4), 737-744

Asymmetric nucleophilic synthesis of 6-[F-18]fluoro-L-dopa was investigated in order to reach an enantiomeric excess of close to 100% of the L form of this amino acid. The radiochemical synthesis required ... [more ▼]

Asymmetric nucleophilic synthesis of 6-[F-18]fluoro-L-dopa was investigated in order to reach an enantiomeric excess of close to 100% of the L form of this amino acid. The radiochemical synthesis required [F-18]fluoride as fluorinating agent and regioselective nucleophilic substitution of commercially available 6-nitroveratraldehyde. The [F-18]fluorobenzaldehyde thus obtained was easily converted to the corresponding 2-[F-18]fluoro-4,5-dimethoxybenzyl bromide. This alkylating agent was added to the lithium enolates of 1-(S)-(-)camphor imine of t-butyl glycinate (1) and (S)-(-)- 1 -Boc-2-t-butyl-3-methyl-4-imidazolidinone [(S)- Boc-BMI] (2) in order to compare the enantiomeric excess of the L form obtained in each case with these two chiral inductors. The L-isomer of fluorodopa was isolated after H1 hydrolysis and HPLC purification in 5-10% radiochemical yield (decay corrected). The overall synthesis time was of 110 min. Through this synthetic pathway, the L-isomer of fluorodopa was obtained in 83% e.e with 1 and 96% e.e with 2 respectively, as determined by chiral HPLC. A practical three step preparative scale synthesis of 6-[F-19]fluoro-D,L-dopa is also presented. [less ▲]

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See detailSYNTHESIS OF NONACTIVATED F-18 FLUORINATED AROMATIC-COMPOUNDS THROUGH NUCLEOPHILIC-SUBSTITUTION AND DECARBOXYLATION REACTIONS
Plenevaux, Alain ULg; Lemaire, Christian ULg; Palmer, Anthtony J. et al

in Applied Radiation & Isotopes (1992), 43(8), 1035-1040

The synthesis of no-carrier-added 3-[F-18]fluoroanisole, 2-[F-18]fluoroanisole, [F-18]fluorobenzene and 4-[F-18]fluoroveratrole are reported. The strategy consists of amino-polyether supported ... [more ▼]

The synthesis of no-carrier-added 3-[F-18]fluoroanisole, 2-[F-18]fluoroanisole, [F-18]fluorobenzene and 4-[F-18]fluoroveratrole are reported. The strategy consists of amino-polyether supported nucleophilic substitution with [F-18]F- on activated nitro aromatic aldehyde precursors followed by decarbonylation using Tris(triphenylphosphine) rhodium (I) chloride. The experimental parameters for this reaction have been studied and optimized with 2-[F-18]fluoro-4-methoxybenzaldehyde and then successfully applied to four other F-18-fluorinated aromatic aldehydes. The decarbonylation yields obtained were 84 +/- 5% (corrected for decay) within 15 min at 150-degrees-C in 1,4-dioxan. [less ▲]

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