Claude Brihaye
University of Liège
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Nuclear Medicine and Biology | 1998
D Le Bars; Christian Lemaire; N. Ginovart; Alain Plenevaux; J. Aerts; Claude Brihaye; Wadad Hassoun; Vincent Leviel; P. Mekhsian; D. Weissmann; Jean-François Pujol; André Luxen; D. Comar
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.
Journal of Labelled Compounds and Radiopharmaceuticals | 1999
Christian Lemaire; Alain Plenevaux; J. Aerts; G. Del Fiore; Claude Brihaye; D. Le Bars; D. Comar; André Luxen
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
Archive | 1993
Christian Crouzel; J.C. Clark; Claude Brihaye; Bengt Långström; Christian Lemaire; Geerd J. Meyer; Bruno Nebeling; Sharon Stone-Elander
Methodological approaches to automation for PET radiochemistry are discussed. Detailed examples of automation using i) simple remote control, ii) PLC-operated devices and iii) computer-controlled devices are described for the syntheses of 11C-, 15O- and 18F-labelled radiopharmaceuticals. Approaches to robot-based automation are also discussed and exemplified.
Journal of Neurochemistry | 2002
Alain Plenevaux; D. Weissmann; J. Aerts; Christian Lemaire; Claude Brihaye; Christian Degueldre; D Le Bars; D. Comar; Jean-François Pujol; André Luxen
The in vivo behavior of 4‐(2′‐methoxyphenyl)‐1‐[2′‐[N‐(2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethyl]‐piperazine (p‐[18F]MPPF), a new serotonin 5‐HT1A 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‐[18F]MPPF and in vitro 8‐hydroxy‐2‐(di‐n‐[3H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p‐[18F]MPPF labeling is (a) in total agreement with the known distribution of 5‐HT1A receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p‐[18F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5‐HT1A specificity of p‐[18F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5‐HT1A binding sites in the brain.
Nuclear Medicine and Biology | 2000
Alain Plenevaux; Christian Lemaire; Joël Aerts; Goran Lacan; Daniel J Rubins; William P. Melega; Claude Brihaye; Christian Degueldre; Sonia Fuchs; Eric Salmon; Pierre Maquet; Steven Laureys; Philippe Damhaut; D. Weissmann; D. Le Bars; Jean Francois Pujol; André Luxen
Abstract This paper summarizes the present status of the researches conducted with [ 18 F]4-(2′-methoxyphenyl)-1-[2′-[ N -(2′′-pyridinyl)- p -fluorobenzamido]ethyl]-piperazine known as [ 18 F] p -MPPF, a new 5-HT 1A antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.
International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes | 1990
Alain Plenevaux; Marcel Guillaume; Claude Brihaye; Christian Lemaire; R. Cantineau
The Ge(4He, xn) and 75As(p, 3n) reactions were compared as the best potential routes for routine production of selenium-73 (73Se) for medical applications. With 26 MeV alpha particles, available with compact cyclotrons, the first reaction required an enriched 70Ge target of sodium metagermanate to give a production yield of 1 mCi/microAh (0.037 GBq/microAh) in a 105 mg/cm2 target. With 55 MeV protons the As(p, 3n) reaction on natural arsenic yielded 20 mCi/microAh (0.74 GBq/microAh) in a 685 mg/cm2 target. A simple method was developed and optimized for both targets in order to isolate and purify the no-carrier-added selenium in the elemental form with a radiochemical yield greater than 75% in less than 90 min. An automated radiochemical processing unit has been designed for the routine production of 100-150 mCi (3.7-5.5 GBq) batches of carrier-free 73Se ready for radiopharmaceutical labeling. 30 mCi (1.11 GBq) (EOS) of L-2-amino-4-([73Se]methylseleno) butyric acid (L-[73Se]selenomethionine) ready for injection with a specific activity of 5 Ci/mmol (185 GBq/mmol) (EOS) were obtained through a fast chemical synthesis. Radiation absorbed dose estimates for L-[73Se]selenomethionine have been determined. A value of 0.70 rem/mCi (0.19 mSv/MBq) administered was calculated for the risk from irradiation in man. The first human PET investigation with [73Se]selenomethionine showed a very good delineation between liver and pancreas.
Tetrahedron | 1997
Philippe Damhaut; Christian Lemaire; Alain Plenevaux; Claude Brihaye; Léon L. Christiaens; D. Comar
Abstract 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 = I)]. After alkylation of the lithium enolate of (2S,5S)-1-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.
International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes | 1989
Claude Brihaye; S. Dewez; Marcel Guillaume; Alvin P. Callahan; D.E. Rice; Furn F. Knapp
Abstract The production of osmium-191 by thermal neutron irradiation of enriched osmium-190 has been evaluated at neutron flux values from 4 × 10 14 to 2.5 × 10 15 neutron cm −2 s −1 in the Oak Ridge High Flux Isotope Reactor (HFIR), the High Flux Brookhaven Reactor (HFBR), and the BR2 reactor in Mol, Belgium. The production route has been analyzed and the cross section values evaluated. The existence of a secondary reaction 191 Os(n, γ) 192 Os with a cross section value of 740 barn has been demonstrated. In order to obtain 191 Os with a specific activity of 250 mCi/mg 190 Os, irradiation periods at neutron flux values lower than 2.5 × 10 15 neutron cm −2 s −1 have to be extended up to 2–4 weeks. This results in significantly increased levels of the undesirable 192 Ir. The 192 Ir is produced by capture of a neutron by 191 Ir, which is formed by decay of the short-lived 4.96 s 191m Ir daughter produced by β-decay of 191 Os. Elution of even small levels of 192 Ir from the 191 Os/ 191m Ir generator results in a large proportion of the total absorbed radiation dose from the generator eluate. Purification of 191 Os by conversion to osmium tetroxide and isolation by both distillation and solvent extraction methods has been developed for the efficient removal of 192 Ir.
International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology | 1988
Furn F. Knapp; Thomas A. Butler; Claude Brihaye
A generator system to provide iridium-191m for clinical imaging applications comprises an activated carbon adsorbent loaded with a compound containing the parent nuclide, osmium-191. The generator, which has a shelf-life in excess of two weeks and does not require a scavenger column, can be eluted with physiologically compatible saline.
International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology | 1990
Alain Plenevaux; R. Cantineau; Claude Brihaye; Christian Lemaire; L. Christiaens; Marcel Guillaume
Four new tertiary amines: bis(3-N,N-dimethyl aminopropyl)selenide (PROMOSE), bis(3-N-(morpholino)propyl)selenide, N-methyl-selenomorpholine and N-phenyl-selenomorpholine structurally related to MOSE proposed by Kung and Blau, have been labeled through a radiochemical procedure suitable for both 75Se and 73Se. The radiochemical yields of the carrier added synthesis ranged between 64 and 85% for the four 75Se labelings and was 64% EOB time corrected for [73Se]PROMOSE. The chemical and radiochemical purities were higher than 99% after chromatographic purifications. The n-octanol/phosphate buffer partition coefficients (P) were measured at various pH (6.5-8) for each compound and the tissue distributions of PROMOSE in rats were also carried out. The experimental results showed a good correlation between the P = f(pH) function and the in vivo behaviour of the considered compound. PROMOSE was selected for further investigations as a brain pH indicator.