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Bertrand Kuhnast - One of the best experts on this subject based on the ideXlab platform.
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Fluorine-18 radiolabeling of biologics
Fluorine in Life Sciences: Pharmaceuticals Medicinal Diagnostics and Agrochemicals, 2019Co-Authors: Simon Specklin, Fabien Caillé, Mélanie Roche, Bertrand KuhnastAbstract:Abstract Biologics-based radiopharmaceuticals, i.e., biological components, including peptides, proteins, polysaccharides, and nucleic acids and their combinations, are increasingly introduced in preclinical and clinical molecular imaging procedures. Synthetically prepared, extracted from natural sources, selected from biological processes, or products of cutting-edge biotechnologies, they all together represent an almost unlimited pool of radiopharmaceutical candidates. No other class of molecules offers the range of chemical diversity that biologics possess. This rich nature's toolkit uncovers a wide range of functions or dysfunctions of the human body with often incomparable potency. The downside is nevertheless that their particular chemical structures and the diversity of chemical functions they bear imply specific radiolabeling approaches. This book chapter will review the existing methods to radiolabel biologics with Fluorine-18, with a particular focus on the most recent bioorthogonal conjugation approaches and strategies derived from chemical biology. An outlook to the direct in vivo labeling possibilities will also be given.
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Synthesis of Fluorine-18-labelled TSPO ligands for imaging neuroinflammation with Positron Emission Tomography
Journal of Fluorine Chemistry, 2012Co-Authors: Dirck Roeda, Bertrand Kuhnast, Annelaure Damont, Frederic DolleAbstract:Abstract Fluorine-18 radiochemistry is an essential tool in Positron Emission Tomography, providing the bridge between the cyclotron-produced raw radioisotope and the biomedical image of an in vivo radioactivity distribution. From the Fluorine-18 labelled radioligands for the translocator protein 18 kDa that are produced in our laboratory, namely [ 18 F]FEDAA1106, 6-[ 18 F]F-PBR28, [ 18 F]PBR111 and [ 18 F]DPA-714, we address various aspects of Fluorine-18 radiochemistry, such as rationales of radiotracer design, radioisotope production and [ 18 F]fluoride activation, and procedures of radiofluorination, purification and formulation. Automation of the radiochemistry process has become indispensable in order to assure a constant radiopharmaceutical quality and reproducible radiochemical yields as well as to meet the required radiation protection aspects.
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Fluorine‐18 Chemistry for Molecular Imaging with Positron Emission Tomography
Fluorine and Health, 2008Co-Authors: Frederic Dolle, Dirck Roeda, Bertrand Kuhnast, Marieclaire LasneAbstract:Publisher Summary Positron emission tomography (PET) is a high-resolution, sensitive, functional-imaging technique in nuclear medicine that permits repeated, non-invasive assessment, and quantification of specific biological and pharmacological processes at the molecular level in humans and animals. It is the most advanced technology currently available for studying in vivo molecular interactions in terms of distribution, pharmacokinetics, and pharmacodynamics. Molecular PET imaging requires the preparation of a positron-emitting radiolabeled probe or radiotracer. For this purpose, Fluorine-18 is becoming increasingly the radionuclide of choice not only due to its adequate physical and nuclear characteristics but also due to the successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical and manifestly a motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. This chapter addresses this complex interdisciplinary and rapidly growing field from a radiochemist point of view, focusing on the synthesis of Fluorine-18-labelled radiopharmaceuticals. The successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical, is manifestly also the motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. The use of Fluorine-18, however, presents some drawbacks in particular the limited options in labeling strategies. The synthesis of complex structures labeled with Fluorine-18 remains a challenge but undoubtedly, Fluorine-18 is already, and will continue to be, a royal gateway to success in molecular imaging with PET.
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Fluorine-18 labelling of small interfering RNAs (siRNAs) for PET imaging†
Journal of Labelled Compounds and Radiopharmaceuticals, 2007Co-Authors: Thomas Viel, Bertrand Kuhnast, Bertrand Tavitian, Françoise Hinnen, Raphaël Boisgard, Frederic DolleAbstract:Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single-stranded ribonucleic acids of short sequences, have been labelled with the positron-emitter Fluorine-18 (T1/2: 109.8 min). The strategy involves (1) prosthetic conjugation of a single-stranded oligonucleotide with [18F]FPyBrA (N-[3-(2-[18F]fluoropyridin-3-yloxy)-propyl]-2-bromoacetamide) followed by (2) formation of the target duplex by annealing with the complementary sequence, therefore, permitting parallel and combinatorial preparation of [18F]siRNAs. Pure Fluorine-18-labelled siRNAs (0.55–1.11 GBq, specific activity: 74–148 GBq/µmol at EOB) could be obtained within 165 min starting from 37.0 GBq of starting [18F]fluoride (1.5–3.0%, non-decay-corrected isolated yields). Copyright © 2007 John Wiley & Sons, Ltd.
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Fluorine-18 labelling of PNAs functionalized at their pseudo-peptidic backbone for imaging studies with PET
Journal of Labelled Compounds and Radiopharmaceuticals, 2004Co-Authors: Bertrand Kuhnast, Bertrand Tavitian, Raphaël Boisgard, F. Hinnen, Ramin Hamzavi, Peter E. Nielsen, F. DolleAbstract:Peptide nucleic acids (PNAs) form a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double-stranded DNA, where the deoxyribose phosphate backbone of original DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while retaining the nucleobases of DNA. We have previously developed an original method to label oligonucleotide-based macromolecules with the short-lived positron-emitter Fluorine-18 (t1/2: 109.8 min) using the N-(4-[18F]fluorobenzyl)-2-bromoacetamide reagent. Using this method, we herein report the Fluorine-18-labelling of 13 decameric PNAs (OLP_1-13), of the same sequence (CTCATACTCT), but presenting selected modification of the pseudo-peptidic backbone at two or three of the thymine residues (positions 2, 5 and 8). Structural characteristics of these backbone modifications include either an amino acid side chain (L-Lys, L-Glu, L-Leu and L-Arg) or a glycosyl moiety (mannose, galactose, fucose, N-Ac-galactosamine and N-Ac-glucosamine) attached via an appropriate spacer. N-(4-[18F]fluorobenzyl)-2-bromoacetamide was synthesized in three radiochemical steps from 4-cyano-N,N,N-trimethylanilinium trifluoromethanesulfonate and HPLC-purified in 85–90 min (typical production: 3.7–4.8 GBq starting from a batch of 29.6–31.4 GBq of [18F]fluoride). Conjugation of the Fluorine-18-labelled bromoacetamide reagent with the PNAs was performed in a mixture of acetonitrile and HEPES buffer (0.1 M, pH 7.9) for 10 min at 60°C and gave the corresponding pure labelled conjugated PNAs ([18F]c-OLP_1-13) after RP-HPLC purification. The whole synthetic procedure, including the preparation of the Fluorine-18-labelled reagent, provides up to 0.9 GBq (25 mCi) of HPLC-purified [18F]c-OLP_1-13 in 160 min with a specific radioactivity of 45–65 GBq/µmol (1.2–1.7 Ci/µmol) at the end of synthesis starting from 29.6 to 31.4 GBq (800–850 mCi) of [18F]fluoride. Copyright © 2004 John Wiley & Sons, Ltd.
Frederic Dolle - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of Fluorine-18-labelled TSPO ligands for imaging neuroinflammation with Positron Emission Tomography
Journal of Fluorine Chemistry, 2012Co-Authors: Dirck Roeda, Bertrand Kuhnast, Annelaure Damont, Frederic DolleAbstract:Abstract Fluorine-18 radiochemistry is an essential tool in Positron Emission Tomography, providing the bridge between the cyclotron-produced raw radioisotope and the biomedical image of an in vivo radioactivity distribution. From the Fluorine-18 labelled radioligands for the translocator protein 18 kDa that are produced in our laboratory, namely [ 18 F]FEDAA1106, 6-[ 18 F]F-PBR28, [ 18 F]PBR111 and [ 18 F]DPA-714, we address various aspects of Fluorine-18 radiochemistry, such as rationales of radiotracer design, radioisotope production and [ 18 F]fluoride activation, and procedures of radiofluorination, purification and formulation. Automation of the radiochemistry process has become indispensable in order to assure a constant radiopharmaceutical quality and reproducible radiochemical yields as well as to meet the required radiation protection aspects.
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Fluorine-18 Chemistry for PET: A Concise Introduction
Current Radiopharmaceuticalse, 2010Co-Authors: Samuel D. Banister, Dirck Roeda, Frederic Dolle, Michael KassiouAbstract:Fluorine-18 is the most important radionuclide used in positron emission tomography (PET) today, largely due to its attractive physical and nuclear characteristics. Agents such as the clinical oncology tracer 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most widely used PET-radiopharmaceutical, are driving an increasing interest in the chemistry of radiopharmaceuticals utilizing Fluorine-18. This review outlines the methods for production of Fluorine-18, and the development of agents for performing radiofluorination reactions. With a few exceptions, radiofluorinations can be classified as either electrophilic or nucleophilic. The electrophilic reactions mainly use molecular [18F]Fluorine of moderately low specific radioactivity, or reagents prepared from it, and include additions to alkenes, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation. The nucleophilic reactions usually involve no-carrier-added (high-specific- radioactivity) [18F]fluoride as its K[18F]F-K222 complex and include SN2-type substitutions in the aliphatic series and SNAr-type substitutions in the aromatic and heteroaromatic series. Key examples from each class of radiofluorination reaction will be described, highlighting the potential of this radioisotope in the design and preparation of Fluorine-18- labeled probes for PET imaging.
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Fluorine‐18 Chemistry for Molecular Imaging with Positron Emission Tomography
Fluorine and Health, 2008Co-Authors: Frederic Dolle, Dirck Roeda, Bertrand Kuhnast, Marieclaire LasneAbstract:Publisher Summary Positron emission tomography (PET) is a high-resolution, sensitive, functional-imaging technique in nuclear medicine that permits repeated, non-invasive assessment, and quantification of specific biological and pharmacological processes at the molecular level in humans and animals. It is the most advanced technology currently available for studying in vivo molecular interactions in terms of distribution, pharmacokinetics, and pharmacodynamics. Molecular PET imaging requires the preparation of a positron-emitting radiolabeled probe or radiotracer. For this purpose, Fluorine-18 is becoming increasingly the radionuclide of choice not only due to its adequate physical and nuclear characteristics but also due to the successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical and manifestly a motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. This chapter addresses this complex interdisciplinary and rapidly growing field from a radiochemist point of view, focusing on the synthesis of Fluorine-18-labelled radiopharmaceuticals. The successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical, is manifestly also the motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. The use of Fluorine-18, however, presents some drawbacks in particular the limited options in labeling strategies. The synthesis of complex structures labeled with Fluorine-18 remains a challenge but undoubtedly, Fluorine-18 is already, and will continue to be, a royal gateway to success in molecular imaging with PET.
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Fluorine-18 labelling of small interfering RNAs (siRNAs) for PET imaging†
Journal of Labelled Compounds and Radiopharmaceuticals, 2007Co-Authors: Thomas Viel, Bertrand Kuhnast, Bertrand Tavitian, Françoise Hinnen, Raphaël Boisgard, Frederic DolleAbstract:Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single-stranded ribonucleic acids of short sequences, have been labelled with the positron-emitter Fluorine-18 (T1/2: 109.8 min). The strategy involves (1) prosthetic conjugation of a single-stranded oligonucleotide with [18F]FPyBrA (N-[3-(2-[18F]fluoropyridin-3-yloxy)-propyl]-2-bromoacetamide) followed by (2) formation of the target duplex by annealing with the complementary sequence, therefore, permitting parallel and combinatorial preparation of [18F]siRNAs. Pure Fluorine-18-labelled siRNAs (0.55–1.11 GBq, specific activity: 74–148 GBq/µmol at EOB) could be obtained within 165 min starting from 37.0 GBq of starting [18F]fluoride (1.5–3.0%, non-decay-corrected isolated yields). Copyright © 2007 John Wiley & Sons, Ltd.
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Chemistry of β +-Emitting Compounds Based on Fluorine-18
Topics in Current Chemistry, 2002Co-Authors: Marieclaire Lasne, Cecile Perrio, Jacques Rouden, Louisa Barre, Dirck Roeda, Frederic Dolle, C CrouzelAbstract:Positron emission tomography (PET) is a non-invasive imaging technology which provides a unique window on the physiology and function of living organisms. It uses short-lived positron emitting isotopes to trace labelled compounds in vivo. Among those radioisotopes, Fluorine-18 is a nuclide of choice: it has a longer half-life (110 min) and a positron energy (0.635 MeV) lower than the other commonly used positron emitter, carbone-11 (t1/2: 20 min, 0.96 MeV). This makes Fluorine-18 very attractive in terms of synthesis time, biological studies and resolutions of PET scans. Fluorine-18 is generally produced in a cyclotron via the 20Ne(d, α)18F or 18O(p,n)18F nuclear reactions. The availability of either labelled molecular Fluorine [18F]F2 or labelled fluoride [18F]F- allows flexibility in the development of synthetic routes to organic compounds. However, [18F]fluoride which is available in high specific activity is preferred for most tracer applications. The aim of this review is to emphasise the scopes and limitations of the chemistry with Fluorine-18. The synthetic methodology of the different 18F-labelled precursors, their uses in rapid reactions and the potential applications of the new 18F-radiopharmaceuticals are reviewed. Apart from basic publications, most references cited have been published in the past 10 years.
F. Dolle - One of the best experts on this subject based on the ideXlab platform.
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Fluorine-18-labelled fluoropyridines: advances in radiopharmaceutical design.
Current Pharmaceutical Design, 2005Co-Authors: F. DolleAbstract:Positron Emission Tomography is a high-resolution, sensitive, functional imaging technique, which can efficiently give access to the distribution, pharmacokinetics and -dynamics of a drug in vivo and which can therefore advantageously play a key-role in both drug discovery and development. This molecular imaging technique requires the preparation of a positron-emitting radiolabelled probe or radiotracer and for this purpose, Fluorine-18 is becoming, more and more often, the radionuclide of choice (adequate physical and nuclear characteristics and potential wide use and -distribution of Fluorine-18-labelled radiopharmaceuticals). Considering chemical structures showing a fluoropyridinyl moiety, nucleophilic heteroaromatic substitution at the ortho-position with no-carrier-added [18F]fluoride appears today as the most efficient method for the radiosynthesis of radiotracers and radiopharmaceuticals of high specific radioactivity when compared to homoaromatic-, but also aliphatic, nucleophilic radiofluorination. Like for the aliphatic nucleophilic radiofluorinations, only a good leaving group is required (a halogen, or better a nitro- or a trimethylammonium group). There is no need for an additional strong electron-withdrawing substituent for activation of the aromatic ring such as in the homoaromatic nucleophilic radiofluorinations, except if one considers meta-fluorination. Nucleophilic heteroaromatic substitution and consequent Fluorine-18 incorporation are generally performed in DMSO with the no-carrier-added, activated K[18F]F-K222 complex using conventional heating at a moderately high temperature (120-150 degrees C) or microwave irradiation (100 Watt) for a short period of time (1-2 minutes) and often lead to high radiochemical yields. This review summarizes some of the recent applications of these nucleophilic heteroaromatic substitutions in the pyridine series and highlights its potential in the design (not seldom by hydrogen, hydroxyl or halogen replacement by Fluorine) and preparation, of often drug-based, Fluorine-18-labelled radiotracers and radiopharmaceuticals of high specific radioactivity for PET imaging.
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Fluorine-18 labelling of PNAs functionalized at their pseudo-peptidic backbone for imaging studies with PET
Journal of Labelled Compounds and Radiopharmaceuticals, 2004Co-Authors: Bertrand Kuhnast, Bertrand Tavitian, Raphaël Boisgard, F. Hinnen, Ramin Hamzavi, Peter E. Nielsen, F. DolleAbstract:Peptide nucleic acids (PNAs) form a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double-stranded DNA, where the deoxyribose phosphate backbone of original DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while retaining the nucleobases of DNA. We have previously developed an original method to label oligonucleotide-based macromolecules with the short-lived positron-emitter Fluorine-18 (t1/2: 109.8 min) using the N-(4-[18F]fluorobenzyl)-2-bromoacetamide reagent. Using this method, we herein report the Fluorine-18-labelling of 13 decameric PNAs (OLP_1-13), of the same sequence (CTCATACTCT), but presenting selected modification of the pseudo-peptidic backbone at two or three of the thymine residues (positions 2, 5 and 8). Structural characteristics of these backbone modifications include either an amino acid side chain (L-Lys, L-Glu, L-Leu and L-Arg) or a glycosyl moiety (mannose, galactose, fucose, N-Ac-galactosamine and N-Ac-glucosamine) attached via an appropriate spacer. N-(4-[18F]fluorobenzyl)-2-bromoacetamide was synthesized in three radiochemical steps from 4-cyano-N,N,N-trimethylanilinium trifluoromethanesulfonate and HPLC-purified in 85–90 min (typical production: 3.7–4.8 GBq starting from a batch of 29.6–31.4 GBq of [18F]fluoride). Conjugation of the Fluorine-18-labelled bromoacetamide reagent with the PNAs was performed in a mixture of acetonitrile and HEPES buffer (0.1 M, pH 7.9) for 10 min at 60°C and gave the corresponding pure labelled conjugated PNAs ([18F]c-OLP_1-13) after RP-HPLC purification. The whole synthetic procedure, including the preparation of the Fluorine-18-labelled reagent, provides up to 0.9 GBq (25 mCi) of HPLC-purified [18F]c-OLP_1-13 in 160 min with a specific radioactivity of 45–65 GBq/µmol (1.2–1.7 Ci/µmol) at the end of synthesis starting from 29.6 to 31.4 GBq (800–850 mCi) of [18F]fluoride. Copyright © 2004 John Wiley & Sons, Ltd.
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Fluorine‐18 labelling of PNAs functionalized at their pseudo‐peptidic backbone for imaging studies with PET
Journal of Labelled Compounds and Radiopharmaceuticals, 2004Co-Authors: Bertrand Kuhnast, Bertrand Tavitian, Françoise Hinnen, Raphaël Boisgard, Ramin Hamzavi, Peter E. Nielsen, F. DolleAbstract:Peptide nucleic acids (PNAs) form a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double-stranded DNA, where the deoxyribose phosphate backbone of original DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while retaining the nucleobases of DNA. We have previously developed an original method to label oligonucleotide-based macromolecules with the short-lived positron-emitter Fluorine-18 (t1/2: 109.8 min) using the N-(4-[18F]fluorobenzyl)-2-bromoacetamide reagent. Using this method, we herein report the Fluorine-18-labelling of 13 decameric PNAs (OLP_1-13), of the same sequence (CTCATACTCT), but presenting selected modification of the pseudo-peptidic backbone at two or three of the thymine residues (positions 2, 5 and 8). Structural characteristics of these backbone modifications include either an amino acid side chain (L-Lys, L-Glu, L-Leu and L-Arg) or a glycosyl moiety (mannose, galactose, fucose, N-Ac-galactosamine and N-Ac-glucosamine) attached via an appropriate spacer. N-(4-[18F]fluorobenzyl)-2-bromoacetamide was synthesized in three radiochemical steps from 4-cyano-N,N,N-trimethylanilinium trifluoromethanesulfonate and HPLC-purified in 85–90 min (typical production: 3.7–4.8 GBq starting from a batch of 29.6–31.4 GBq of [18F]fluoride). Conjugation of the Fluorine-18-labelled bromoacetamide reagent with the PNAs was performed in a mixture of acetonitrile and HEPES buffer (0.1 M, pH 7.9) for 10 min at 60°C and gave the corresponding pure labelled conjugated PNAs ([18F]c-OLP_1-13) after RP-HPLC purification. The whole synthetic procedure, including the preparation of the Fluorine-18-labelled reagent, provides up to 0.9 GBq (25 mCi) of HPLC-purified [18F]c-OLP_1-13 in 160 min with a specific radioactivity of 45–65 GBq/µmol (1.2–1.7 Ci/µmol) at the end of synthesis starting from 29.6 to 31.4 GBq (800–850 mCi) of [18F]fluoride. Copyright © 2004 John Wiley & Sons, Ltd.
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Fluorine‐18‐ and iodine‐125‐labelling of spiegelmers
Journal of Labelled Compounds and Radiopharmaceuticals, 2003Co-Authors: Bertrand Kuhnast, Françoise Hinnen, Raphaël Boisgard, Sven Klussmann, Bernard Rousseau, Jens Peter Fürste, B. Tavitian, F. DolleAbstract:Spiegelmers are high-affinity l-enantiomeric oligonucleotide ligands (aptamers) that display high resistance to enzymatic degradation compared to d-oligonucleotides. Spiegelmers belong to the third generation of aptamers, and are currently extensively investigated as potential therapeutic agents. We have previously developed an original method to label natural oligonucleotides with radiohalogens and particularly with Fluorine-18, the most widely used positron-emitter, t1/2: 109.8 min. Using the same strategy, we herein report the labelling of Spiegelmers, both with Fluorine-18 for positron emission tomography imaging and iodine-125 for high resolution autoradiography. Three 25-mer l-oligonucleotides have been used, differing (a) by the position of the terminal phosphorothioate monoester group (3′- or 5′-end, and therefore differing by the position of the labelling on the macromolecule) and (b) by the nature of the backbone sugar moiety (2′-OH or 2′-H, therefore covering the RNA and DNA series, respectively). N-(4-[18F]fluorobenzyl)-2-bromoacetamide was synthesized in three radiochemical steps from 4-cyano-N,N,N-trimethylanilinium trifluoromethanesulfonate and HPLC-purified in 90 min (typical production: 2.2–2.4 GBq starting from a batch of 22–24 GBq of [18F]fluoride). N-(4-[125I]iodobenzyl)-2-bromoacetamide was synthesized from the corresponding trimethylsilyl derivative (one pot, two radiochemical steps) and HPLC-purified in 60 min (typical production: 24 MBq starting from 37 MBq of Na[125I]I). Coupling of the Spiegelmers with the appropriate HPLC-purified [radiolabelled]-halobenzyl-2-bromoacetamide (MeOH/PBS (0.1 M, pH 8), 10 min, 120°C) gave the corresponding labelled conjugated Spiegelmers after RP-HPLC purification. For Fluorine-18, the whole synthetic procedure yields up to 1.1 GBq of pure labelled Spiegelmers in 160 min with a specific radioactivity of 37–74 GBq/μmol at the end of synthesis starting from 22–24 GBq of [18F]fluoride. For iodine-125, the whole synthetic procedure allows producing up to 7.4 MBq of pure labelled Spiegelmers in 100 min with a specific radioactivity of 11–37 GBq/μmol starting from 37 MBq of Na[125I]I. Copyright © 2003 John Wiley & Sons, Ltd.
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Fluorine‐18 labelling of oligonucleotides: Prosthetic labelling at the 5′‐end using the N‐(4‐[18F]fluorobenzyl)‐2‐bromoacetamide reagent
Journal of Labelled Compounds and Radiopharmaceuticals, 2003Co-Authors: Bertrand Kuhnast, Françoise Hinnen, Raphaël Boisgard, B. Tavitian, F. DolleAbstract:Labelled oligonucleotides are new imaging tools to study gene expression at the nucleic acid and protein levels. We have previously developed a universal method to label oligonucleotides at their 3′-end with radiohalogens and particularly with Fluorine-18, the most widely used positron-emitter, t1/2: 109.8 min. Using the same strategy, we herein report the Fluorine-18 labelling of oligonucleotides at their 5′-end. A 18-mer 2′O-methyl modified oligoribonucleotide, bearing a phosphorothioate group at its 5′-end, was conjugated to our Fluorine-18-labelled reagent N-(4-[18F]fluorobenzyl)-2-bromoacetamide. The whole synthetic procedure yielded up to 1 GBq of Fluorine-18-labelled oligonucleotide with a specific radioactivity of 37–74 GBq/μmol in 160 min. Copyright © 2003 John Wiley & Sons, Ltd.
Alan Salama - One of the best experts on this subject based on the ideXlab platform.
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uptake of Fluorine 18 fluorodeoxyglucose in sarcoidosis
The Journal of Nuclear Medicine, 1994Co-Authors: Penney Lewis, Alan SalamaAbstract:Whole-body PET scanning was performed using {sup 18}F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of {sup 18}FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy. 30 refs., 3 figs.
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Uptake of Fluorine-18-Fluorodeoxyglucose in Sarcoidosis
Journal of nuclear medicine : official publication Society of Nuclear Medicine, 1994Co-Authors: Petra J. Lewis, Alan SalamaAbstract:Whole-body PET scanning was performed using 18F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of 18FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy.
Dirck Roeda - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of Fluorine-18-labelled TSPO ligands for imaging neuroinflammation with Positron Emission Tomography
Journal of Fluorine Chemistry, 2012Co-Authors: Dirck Roeda, Bertrand Kuhnast, Annelaure Damont, Frederic DolleAbstract:Abstract Fluorine-18 radiochemistry is an essential tool in Positron Emission Tomography, providing the bridge between the cyclotron-produced raw radioisotope and the biomedical image of an in vivo radioactivity distribution. From the Fluorine-18 labelled radioligands for the translocator protein 18 kDa that are produced in our laboratory, namely [ 18 F]FEDAA1106, 6-[ 18 F]F-PBR28, [ 18 F]PBR111 and [ 18 F]DPA-714, we address various aspects of Fluorine-18 radiochemistry, such as rationales of radiotracer design, radioisotope production and [ 18 F]fluoride activation, and procedures of radiofluorination, purification and formulation. Automation of the radiochemistry process has become indispensable in order to assure a constant radiopharmaceutical quality and reproducible radiochemical yields as well as to meet the required radiation protection aspects.
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Fluorine-18 Chemistry for PET: A Concise Introduction
Current Radiopharmaceuticalse, 2010Co-Authors: Samuel D. Banister, Dirck Roeda, Frederic Dolle, Michael KassiouAbstract:Fluorine-18 is the most important radionuclide used in positron emission tomography (PET) today, largely due to its attractive physical and nuclear characteristics. Agents such as the clinical oncology tracer 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most widely used PET-radiopharmaceutical, are driving an increasing interest in the chemistry of radiopharmaceuticals utilizing Fluorine-18. This review outlines the methods for production of Fluorine-18, and the development of agents for performing radiofluorination reactions. With a few exceptions, radiofluorinations can be classified as either electrophilic or nucleophilic. The electrophilic reactions mainly use molecular [18F]Fluorine of moderately low specific radioactivity, or reagents prepared from it, and include additions to alkenes, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation. The nucleophilic reactions usually involve no-carrier-added (high-specific- radioactivity) [18F]fluoride as its K[18F]F-K222 complex and include SN2-type substitutions in the aliphatic series and SNAr-type substitutions in the aromatic and heteroaromatic series. Key examples from each class of radiofluorination reaction will be described, highlighting the potential of this radioisotope in the design and preparation of Fluorine-18- labeled probes for PET imaging.
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Fluorine‐18 Chemistry for Molecular Imaging with Positron Emission Tomography
Fluorine and Health, 2008Co-Authors: Frederic Dolle, Dirck Roeda, Bertrand Kuhnast, Marieclaire LasneAbstract:Publisher Summary Positron emission tomography (PET) is a high-resolution, sensitive, functional-imaging technique in nuclear medicine that permits repeated, non-invasive assessment, and quantification of specific biological and pharmacological processes at the molecular level in humans and animals. It is the most advanced technology currently available for studying in vivo molecular interactions in terms of distribution, pharmacokinetics, and pharmacodynamics. Molecular PET imaging requires the preparation of a positron-emitting radiolabeled probe or radiotracer. For this purpose, Fluorine-18 is becoming increasingly the radionuclide of choice not only due to its adequate physical and nuclear characteristics but also due to the successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical and manifestly a motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. This chapter addresses this complex interdisciplinary and rapidly growing field from a radiochemist point of view, focusing on the synthesis of Fluorine-18-labelled radiopharmaceuticals. The successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), currently the most widely used PET radiopharmaceutical, is manifestly also the motor behind the growing availability and interest for this positron emitter in radiopharmaceutical chemistry. The use of Fluorine-18, however, presents some drawbacks in particular the limited options in labeling strategies. The synthesis of complex structures labeled with Fluorine-18 remains a challenge but undoubtedly, Fluorine-18 is already, and will continue to be, a royal gateway to success in molecular imaging with PET.
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Chemistry of β +-Emitting Compounds Based on Fluorine-18
Topics in Current Chemistry, 2002Co-Authors: Marieclaire Lasne, Cecile Perrio, Jacques Rouden, Louisa Barre, Dirck Roeda, Frederic Dolle, C CrouzelAbstract:Positron emission tomography (PET) is a non-invasive imaging technology which provides a unique window on the physiology and function of living organisms. It uses short-lived positron emitting isotopes to trace labelled compounds in vivo. Among those radioisotopes, Fluorine-18 is a nuclide of choice: it has a longer half-life (110 min) and a positron energy (0.635 MeV) lower than the other commonly used positron emitter, carbone-11 (t1/2: 20 min, 0.96 MeV). This makes Fluorine-18 very attractive in terms of synthesis time, biological studies and resolutions of PET scans. Fluorine-18 is generally produced in a cyclotron via the 20Ne(d, α)18F or 18O(p,n)18F nuclear reactions. The availability of either labelled molecular Fluorine [18F]F2 or labelled fluoride [18F]F- allows flexibility in the development of synthetic routes to organic compounds. However, [18F]fluoride which is available in high specific activity is preferred for most tracer applications. The aim of this review is to emphasise the scopes and limitations of the chemistry with Fluorine-18. The synthetic methodology of the different 18F-labelled precursors, their uses in rapid reactions and the potential applications of the new 18F-radiopharmaceuticals are reviewed. Apart from basic publications, most references cited have been published in the past 10 years.
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chemistry of β emitting compounds based on Fluorine 18
Topics in Current Chemistry, 2002Co-Authors: Marieclaire Lasne, Cecile Perrio, Jacques Rouden, Louisa Barre, Dirck Roeda, Frederic Dolle, C CrouzelAbstract:Positron emission tomography (PET) is a non-invasive imaging technology which provides a unique window on the physiology and function of living organisms. It uses short-lived positron emitting isotopes to trace labelled compounds in vivo. Among those radioisotopes, Fluorine-18 is a nuclide of choice: it has a longer half-life (110 min) and a positron energy (0.635 MeV) lower than the other commonly used positron emitter, carbone-11 (t1/2: 20 min, 0.96 MeV). This makes Fluorine-18 very attractive in terms of synthesis time, biological studies and resolutions of PET scans. Fluorine-18 is generally produced in a cyclotron via the 20Ne(d, α)18F or 18O(p,n)18F nuclear reactions. The availability of either labelled molecular Fluorine [18F]F2 or labelled fluoride [18F]F- allows flexibility in the development of synthetic routes to organic compounds. However, [18F]fluoride which is available in high specific activity is preferred for most tracer applications. The aim of this review is to emphasise the scopes and limitations of the chemistry with Fluorine-18. The synthetic methodology of the different 18F-labelled precursors, their uses in rapid reactions and the potential applications of the new 18F-radiopharmaceuticals are reviewed. Apart from basic publications, most references cited have been published in the past 10 years.