References of "Thonon, David"
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See detailSynthesis of two new alkyne-bearing liners used for the preparation of siRNA for labeling by click chemistry with fluorine-18
Flagothier, Jessica ULg; Kaisin, Geoffroy ULg; Mercier, Frederic et al

in Applied Radiation & Isotopes (2012), 70(8), 1549-1557

Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a ... [more ▼]

Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [18F]labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two news linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [18F]prosthetic group. [less ▲]

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See detailAutomated synthesis of [18F] FBEM for labeling of thiol containing compounds
Paris, Jérôme ULg; Thonon, David ULg; Kaisin, Geoffroy ULg et al

Poster (2011, September 01)

[18F]FBEM, i.e. N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, is a useful synthon employed for the specific radiolabeling of thiol containing compounds, including peptides and proteins. The aim of the ... [more ▼]

[18F]FBEM, i.e. N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, is a useful synthon employed for the specific radiolabeling of thiol containing compounds, including peptides and proteins. The aim of the present work was to develop a fast, reproducible and fully automated synthesis of this compound in order to improve its availabilty as well as for obvious radioprotection matters. [less ▲]

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See detailSynthesis and hydrolytic stability of novel 3-[18F]fluoroethoxybis(1-methylethyl)silyl]propanaminebased prosthetic groups
collet, Charlotte; Lamandé-Langle, Sandrine; Balentova, Eva et al

Poster (2011)

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See detailGadolinium DOTA Chelates Featuring Alkyne Groups Directly Grafted on the Tetraaza Macrocyclic Ring: Synthesis, Relaxation Properties, "Click" Reaction, and High-Relaxivity Micelles
Vanasschen, Christian; Bouslimani, Nouri ULg; Thonon, David ULg et al

in Inorganic Chemistry (2011), 50(18), 8946-8958

This paper reports on the synthesis and relaxivity properties of tetraacetic DOTA-type chelating agents featuring one or two alkyne groups directly grafted on the tetraaza macrocyclic ring and available ... [more ▼]

This paper reports on the synthesis and relaxivity properties of tetraacetic DOTA-type chelating agents featuring one or two alkyne groups directly grafted on the tetraaza macrocyclic ring and available for "click" reactions with azide-bearing substrates. The racemic DOTAma ligand bearing one alkyne group was obtained by a bisaminal template route. The same approach was used to prep. ligand DOTAda substituted by two alkyne groups located on two adjacent carbon atoms. The S,S enantiomer of DOTAda was also prepd. by a "crab-like" condensation. This ligand is the first example of a DOTA deriv. featuring two reactive functions adjacent to each other on the macrocyclic ring. A triacetic monoalkyne ligand (DO3ma) was also synthesized for comparison purposes. NMR studies indicate that the Yb(III) chelates of DOTAma and DOTAda adopt two conformations in solns. in which the tetraaza ring is rigidified. The hydration state of the Eu(III) chelates was detd. by luminescence spectroscopy, and the water exchange time of the Gd(III) complexes was measured by 17O NMR. Ring substitution accelerates the water exchange. These data were used to interpret nuclear magnetic relaxation dispersion curves of the Gd(III) chelates. Two long aliph. chains have been added to DOTAda by a "click" procedure to form the (C18)2DOTAda ligand. The corresponding Gd(III) complex forms micelles of unusually high relaxivity presumably because of the close proximity of the aliph. chains on the macrocyclic ring that ensures a rigid double anchoring into the micelles. [less ▲]

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See detailRadiolabeling of modified siRNA by click chemistry with fluorine-18 for PET studies
Flagothier, Jessica ULg; Mercier, Frédéric; Kaisin, Geoffroy ULg et al

in Journal of Labelled Compounds and Radiopharmaceuticals (2011)

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See detailPhotoclick chemistry: Applications to 18F radiotracers preparation
Thonon, David ULg; Goukens, Eve ULg; Kaisin, Geoffroy ULg et al

in Journal of Labelled Compounds and Radiopharmaceuticals (2011)

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See detailSynthesis and hydrolytic stability of novel 3-[18F]fluoroethoxybis(1-methylethyl)silyl]propanamine-based prosthetic groups
Balentova, Eva; Collet, Charlotte; Lamande-Langle, Sandrine et al

in Journal of Fluorine Chemistry (2011), 132(4), 250-257

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepd. in good yields. These silicon groups bearing an acid or an azide group were coupled to ... [more ▼]

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepd. in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly- Gly) either through a classical amide bond formation or through "click chem." via the Huisgen cycloaddn. The radiolabeling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51-54% decay cor. radiochem. yields. Radiolabeled peptides were easily prepd. by direct 18F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabeled silicon-based prosthetic group. Their stabilities in physiol. medium were studied and proved poor. [less ▲]

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See detailImaging apolipoprotein AI in vivo
Sriram, Renuka; Lagerstedt, Jens; Petrlova, Jitka et al

in NMR in Biomedicine (2011), 24(7), 916-924

Coronary disease risk increases inversely with high-d. lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a tech. challenge. This study ... [more ▼]

Coronary disease risk increases inversely with high-d. lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a tech. challenge. This study presents an approach to the development of a lipoprotein MRI agent by linking gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) to a selective cysteine mutation in position 55 of apo AI, the major protein of HDL. The contrast agent targets both liver and kidney, the sites of HDL catabolism, whereas the std. MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acidbismethylamide (GdDTPA-BMA, gadodiamide), enhances only the kidney image. Using a modified apolipoprotein AI to create an HDL contrast agent provides a new approach to investigate HDL biodistribution, metab. and regulation in vivo. [less ▲]

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See detailFully Automated Preparation and Conjugation of N-Succinimidyl 4-[(18)F]Fluorobenzoate ([ (18)F]SFB) with RGD Peptide Using a GE FASTlab Synthesizer.
Thonon, David ULg; Goblet, D.; Goukens, Eve ULg et al

in Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging (2011)

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab ... [more ▼]

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab, GE Healthcare). PROCEDURES: Two synthesis approaches were implemented on this module: the classical "two-pot radiosynthesis" and the more recently described "one-pot" method. RESULTS: The "two-pot" approach affords [(18)F]SFB with a 42% decay-corrected yield in 57 min (n = 24) with a chemical purity sufficient to avoid an intermediate HPLC purification. The recently established "one-pot" method, afforded a product with a lower chemical purity, in the conditions used in this report. The lower d.c. yield obtained (32% (n = 15)) was related to the low (18)F labeling yields obtained in MeCN compared with DMSO. The subsequent conjugation step with a RGD (PRGD2) peptide was also successfully automated. CONCLUSIONS: The formulated [(18)F]FPRGD2 was obtained without any operator manipulation with a d.c. yield of 13% +/- 3% (n = 13) in 130 min, a radiochemical purity >98% and a specific activity of 140 +/- 40 TBq/mmol. [less ▲]

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See detailGeneral Method for Labeling siRNA by Click Chemistry with Fluorine-18 for the Purpose of PET Imaging
Mercier, Frédéric; Paris, Jérôme ULg; Kaisin, Geoffroy ULg et al

in Bioconjugate Chemistry (2011), 22(1), 108-114

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See detailClick chemistry : radiolabelling of oligonucleotides with fluorine- 18 for PET
Kaisin, Geoffroy ULg; Flagothier, Jessica ULg; Mercier, Frédéric ULg et al

Poster (2010, June)

Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET ... [more ▼]

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.1 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. 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. This also allows the development of universal solid supports used for the solidphase synthesis of ONs. Here we report the synthesis of three alkyne-bearing linkers , the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]- fluorobenzene) and coupling with functionalized ONs. [less ▲]

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See detailAutomated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors
Goblet, David ULg; Thonon, David ULg; Plenevaux, Alain ULg et al

Poster (2010, May 30)

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is ... [more ▼]

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is implicated in numerous neurodegenerative disorders such as Alzheimer disease’s, dementia, depression, anxiety, schizophrenia, and Parkinson disease’s. The 5-HT1A serotonin receptors are involved in several physiological functions including sleep, mood, neurogenesis and learning [1]. Consequently, there have been huge efforts in finding ligands for this receptor. [11C]WAY-100635 is a high affinity radioligand used for quantifying serotonin 5-HT1A receptors with positron emission tomography. An 18F-labeled radioligand is advantageous because of higher specific activity and physical/nuclear properties (t1/2= 109 min, 97% of positron decay and positron energy of 635 keV maximum). [18F]MPPF, a selective 5-HT1A antagonist derived from WAY-100635, is currently one of the most successful PET ligand used for 5-HT1A receptor imaging [2]. However the affinity is lower then WAY-100635 and the amount of [18F]MPPF reaching the brain is relatively low since MPPF is a substrate for p-glycoprotein [3]. Methods: In order to improve the brain uptake of the radiotracer, a desmethylated analog has been developed in our lab and preliminary in vitro studies show positive results [4]. Nevertheless, the radiosynthesis take place in two steps as a protecting group removal is needed. A one step procedure with a MPPF derivative could be of very great interest. We have synthesized many MPPF derivatives in our lab (modification on the phenylpiperazine moiety) and developed an automated radiosynthesis procedure for the production of these radiotracers. [18F]MPPF was chosen as the model compound. We used a GE Healthcare FASTlabTM module and made modifications to the [18F]FDG synthesis sequence and cassette. [18F]MPPF was synthesized by coupling of [18F]FBA with the corresponding amine. After coupling, the crude solution was diluted with water and passed through a tC18 cartridge for prepurification. After elution, the [18F]MPPF was purified by semi-preparative HPLC. Results: Total synthesis time, including purification was approximately 100 min. [18F]FBA and [18F]MPPF were obtained at a corrected yield of 55% (n=20) and 25% (n=5) respectively. The radiochemical purity, checked by radio-TLC and UPLC, was >95%. Conclusions: We have developed an automated method for [18F]MPPF and derivatives production using a commercial synthesizer (FASTlabTM from GE Healthcare) and a conventional HPLC system resulting in good yields and high (radio)chemical purity. By simply switching the vial containing the modified amine, an 18F-labeled MPPF derivative could be obtained. Radiosynthesis is still under optimization and the radiotracers synthesized need to be tested as suitable 5-HT1A radioligands. Acknowledgement: This work was supported by the Fondation Rahier. References: [1] Filip M., Bader M. et Al, Pharmacol Rep. 2009 Sep-Oct; 61(5):761-77 [2] Aznavour N, Zimmer L. Et Al, Neuropharmacology. 2007 Mar; 52(3):695-707 [3] Laćan G., Plenevaux A. et Al, Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66 [4] Defraiteur C., Plenevaux A. et Al., Br J Pharmacol. 2007 Nov; 152(6):952-8 [less ▲]

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See detail18F labelling of Insulin via click chemistry
Paris, Jérôme ULg; Mercier, Frédéric ULg; Thonon, David ULg et al

Poster (2010, May 27)

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See detailFast production of highly concentrated reactive [18F] fluoride for aliphatic and aromatic nucleophilic radiolabelling
Aerts, Joël ULg; Voccia, Samuel; Lemaire, Christian ULg et al

in Tetrahedron Letters (2010), 51

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic ... [more ▼]

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield. [less ▲]

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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

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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

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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)

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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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