Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18kDa) with PET
Identifieur interne : 008A96 ( Main/Exploration ); précédent : 008A95; suivant : 008A97Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18kDa) with PET
Auteurs : Annelaure Damont [France] ; Francoise Hinnen [France] ; Bertrand Kuhnast [France] ; Marie-Anne Schöllhorn-Peyronneau [France] ; Michelle James [Australie] ; Christopher Luus [Australie] ; Bertrand Tavitian [France] ; Michael Kassiouy [Australie] ; Frédéric Dolle [France]Source :
- Journal of labelled compounds & radiopharmaceuticals [ 0362-4803 ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Fluor 18, Sélectivité, Pyrazolopyrimidine dérivé, Agent scintigraphique, Hétérocycle azote angulaire, Composé bicyclique, Dérivé du benzène, Ether, Carboxamide, Fluoration, Récepteur benzodiazépinique périphérique, Synthèse chimique, Marquage radioisotopique, Fluor Isotope, Ligand, Radiosynthèse, Radioligand, Pyrazolo[1,5-a]pyrimidine-3-acétamide(N,N-diéthyl-5,7-diméthyl-2-[4-méthoxyphényl]), Pyrazolo[1,5-a]pyrimidine-3-acetamide(N,N-diéthyl-5,7-diméthyl-2-[4-(2-fluoroéthoxy)phényl]).
English descriptors
- KwdEn :
Abstract
Recently, a novel series of 2-phenylpyrazolo[1,5-a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18kDa). Within this series, DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide, Ki=7.0nM is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine-18 (half-life: 109.8 min) and in vivo imaging using positron emission tomography. DPA-714 and its tosyloxy derivative (N,N-diethyl-2-(2-(4-(2-toluenesulfonyloxyethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-o]pyrimidin-3-yl)acetamide) as precursor for the labelling with fluorine-18 were synthesized in two steps from DPA-713 (N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) and obtained in 32 and 42% yields, respectively. [18F]DPA-714 was synthesized using a simple one-step process (a tosyloxy-for-fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate-XP robotic system. It involves: (A) reaction of K[ F]F-Kryptofix 222 with the tosyloxy precursor (4.5-5.0 mg, 8.2-9.1 μmol) at 165°C for 5 min in dimethyl sufloxide (0.6mL) followed by (B) C18 PrepSep cartridge pre-purification and finally (C) semi-preparative high-performance liquid chromatography (HPLC) purification on a Waters X-Terra<TM> RP18. Typically, 5.6-7.4 GBq of [18F]DPA-714 (>95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111GBq/μmol within 85-90 min (HPLC purification and SepPak®-based formulation included), starting from a 37 GBq [18F]fluoride batch (overall non-decay-corrected and isolated radiochemical yield: 15-20%).
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type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Hinnen, Francoise" sort="Hinnen, Francoise" uniqKey="Hinnen F" first="Francoise" last="Hinnen">Francoise Hinnen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>CEA, 12BM, Service Hospitalier Fréderic Joliot, Laboratoire d'lmagerie Moléculaire Expérimentale</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Kuhnast, Bertrand" sort="Kuhnast, Bertrand" uniqKey="Kuhnast B" first="Bertrand" last="Kuhnast">Bertrand Kuhnast</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>CEA, 12BM, Service Hospitalier Fréderic Joliot, Laboratoire d'lmagerie Moléculaire Expérimentale</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Schollhorn Peyronneau, Marie Anne" sort="Schollhorn Peyronneau, Marie Anne" uniqKey="Schollhorn Peyronneau M" first="Marie-Anne" last="Schöllhorn-Peyronneau">Marie-Anne Schöllhorn-Peyronneau</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>CEA, 12BM, Service Hospitalier Fréderic Joliot, Laboratoire d'lmagerie Moléculaire Expérimentale</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="James, Michelle" sort="James, Michelle" uniqKey="James M" first="Michelle" last="James">Michelle James</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>NSW 2006</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Brain and Mind Research Institute, University of Sydney</s1><s2>NSW 2050</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Luus, Christopher" sort="Luus, Christopher" uniqKey="Luus C" first="Christopher" last="Luus">Christopher Luus</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>NSW 2006</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Brain and Mind Research Institute, University of Sydney</s1><s2>NSW 2050</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Tavitian, Bertrand" sort="Tavitian, Bertrand" uniqKey="Tavitian B" first="Bertrand" last="Tavitian">Bertrand Tavitian</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>CEA, 12BM, Service Hospitalier Fréderic Joliot, Laboratoire d'lmagerie Moléculaire Expérimentale</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM, U803, Service Hospitalier Frédéric Joliot</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Kassiouy, Michael" sort="Kassiouy, Michael" uniqKey="Kassiouy M" first="Michael" last="Kassiouy">Michael Kassiouy</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Brain and Mind Research Institute, University of Sydney</s1><s2>NSW 2050</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Discipline of Medical Radiation Sciences, University of Sydney</s1><s2>NSW 2006</s2><s3>AUS</s3><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>School of Chemistry, University of Sydney</s1><s2>NSW 2006</s2><s3>AUS</s3><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Dolle, Frederic" sort="Dolle, Frederic" uniqKey="Dolle F" first="Frédéric" last="Dolle">Frédéric Dolle</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>CEA, 12BM, Service Hospitalier Fréderic Joliot, Laboratoire d'lmagerie Moléculaire Expérimentale</s1><s2>91401 Orsay</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of labelled compounds & radiopharmaceuticals</title><title level="j" type="abbreviated">J. labelled compd. radiopharm.</title><idno type="ISSN">0362-4803</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of labelled compounds & radiopharmaceuticals</title><title level="j" type="abbreviated">J. labelled compd. radiopharm.</title><idno type="ISSN">0362-4803</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angular nitrogen heterocycle</term><term>Benzene derivatives</term><term>Bicyclic compound</term><term>Carboxamide</term><term>Chemical synthesis</term><term>Ether</term><term>Fluorination</term><term>Fluorine 18</term><term>Fluorine Isotopes</term><term>Ligand</term><term>Peripheral benzodiazepine receptor</term><term>Pyrazolopyrimidine derivatives</term><term>Radiolabelling</term><term>Scintigraphic agent</term><term>Selectivity</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Fluor 18</term><term>Sélectivité</term><term>Pyrazolopyrimidine dérivé</term><term>Agent scintigraphique</term><term>Hétérocycle azote angulaire</term><term>Composé bicyclique</term><term>Dérivé du benzène</term><term>Ether</term><term>Carboxamide</term><term>Fluoration</term><term>Récepteur benzodiazépinique périphérique</term><term>Synthèse chimique</term><term>Marquage radioisotopique</term><term>Fluor Isotope</term><term>Ligand</term><term>Radiosynthèse</term><term>Radioligand</term><term>Pyrazolo[1,5-a]pyrimidine-3-acétamide(N,N-diéthyl-5,7-diméthyl-2-[4-méthoxyphényl])</term><term>Pyrazolo[1,5-a]pyrimidine-3-acetamide(N,N-diéthyl-5,7-diméthyl-2-[4-(2-fluoroéthoxy)phényl])</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recently, a novel series of 2-phenylpyrazolo[1,5-a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18kDa). Within this series, DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide, K<sub>i</sub>=7.0nM is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine-18 (half-life: 109.8 min) and in vivo imaging using positron emission tomography. DPA-714 and its tosyloxy derivative (N,N-diethyl-2-(2-(4-(2-toluenesulfonyloxyethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-o]pyrimidin-3-yl)acetamide) as precursor for the labelling with fluorine-18 were synthesized in two steps from DPA-713 (N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) and obtained in 32 and 42% yields, respectively. [<sup>18</sup>F]DPA-714 was synthesized using a simple one-step process (a tosyloxy-for-fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate-XP robotic system. It involves: (A) reaction of K[ F]F-Kryptofix 222 with the tosyloxy precursor (4.5-5.0 mg, 8.2-9.1 μmol) at 165°C for 5 min in dimethyl sufloxide (0.6mL) followed by (B) C18 PrepSep cartridge pre-purification and finally (C) semi-preparative high-performance liquid chromatography (HPLC) purification on a Waters X-Terra<<sup>TM</sup>> RP18. Typically, 5.6-7.4 GBq of [<sup>18</sup>F]DPA-714 (>95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111GBq/μmol within 85-90 min (HPLC purification and SepPak®-based formulation included), starting from a 37 GBq [<sup>18</sup>F]fluoride batch (overall non-decay-corrected and isolated radiochemical yield: 15-20%).</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Nouvelle-Galles du Sud</li><li>Île-de-France</li></region><settlement><li>Orsay</li><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Damont, Annelaure" sort="Damont, Annelaure" uniqKey="Damont A" first="Annelaure" last="Damont">Annelaure Damont</name></region><name sortKey="Dolle, Frederic" sort="Dolle, Frederic" uniqKey="Dolle F" first="Frédéric" last="Dolle">Frédéric Dolle</name><name sortKey="Hinnen, Francoise" sort="Hinnen, Francoise" uniqKey="Hinnen F" first="Francoise" last="Hinnen">Francoise Hinnen</name><name sortKey="Kuhnast, Bertrand" sort="Kuhnast, Bertrand" uniqKey="Kuhnast B" first="Bertrand" last="Kuhnast">Bertrand Kuhnast</name><name sortKey="Schollhorn Peyronneau, Marie Anne" sort="Schollhorn Peyronneau, Marie Anne" uniqKey="Schollhorn Peyronneau M" first="Marie-Anne" last="Schöllhorn-Peyronneau">Marie-Anne Schöllhorn-Peyronneau</name><name sortKey="Tavitian, Bertrand" sort="Tavitian, Bertrand" uniqKey="Tavitian B" first="Bertrand" last="Tavitian">Bertrand Tavitian</name><name sortKey="Tavitian, Bertrand" sort="Tavitian, Bertrand" uniqKey="Tavitian B" first="Bertrand" last="Tavitian">Bertrand Tavitian</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="James, Michelle" sort="James, Michelle" uniqKey="James M" first="Michelle" last="James">Michelle James</name></region><name sortKey="James, Michelle" sort="James, Michelle" uniqKey="James M" first="Michelle" last="James">Michelle James</name><name sortKey="Kassiouy, Michael" sort="Kassiouy, Michael" uniqKey="Kassiouy M" first="Michael" last="Kassiouy">Michael Kassiouy</name><name sortKey="Kassiouy, Michael" sort="Kassiouy, Michael" uniqKey="Kassiouy M" first="Michael" last="Kassiouy">Michael Kassiouy</name><name sortKey="Kassiouy, Michael" sort="Kassiouy, Michael" uniqKey="Kassiouy M" first="Michael" last="Kassiouy">Michael Kassiouy</name><name sortKey="Luus, Christopher" sort="Luus, Christopher" uniqKey="Luus C" first="Christopher" last="Luus">Christopher Luus</name><name sortKey="Luus, Christopher" sort="Luus, Christopher" uniqKey="Luus C" first="Christopher" last="Luus">Christopher Luus</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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