10867
doi
10.1002/jlcr.3199
oai:zenodo.org:10867
user-inmind
user-eu
Bernards, Nicholas
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France and Inserm, U1023, Université Paris Sud, Orsay, France
Kuhnast, Bertrand
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France
Damont, Annelaure
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France
Pottier, Géraldine
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France and Inserm, U1023, Université Paris Sud, Orsay, France
Peyronneau, Marie-Anne
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France
Kassiou, Michael
School of Chemistry, University of Sydney, Sydney, Australia and Discipline of Medical Radiation Sciences, University of Sydney, Sydney, Australia
Marguet, Frank
Exploratory Unit, Sanofi, Paris, France
Puech, Frédéric
Exploratory Unit, Sanofi, Paris, France
Boisgard, Raphael
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France and Inserm, U1023, Université Paris Sud, Orsay, France
Dollé, Frédéric
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France
[18F]DPA-C5yne, a novel fluorine-18-labelled analogue of DPA-714: radiosynthesis and preliminary evaluation as a radiotracer for imaging neuroinflammation with PET
Médran-Navarrete, Vincent
CEA, I2BM, Service Hospitalier, Frédéric Joliot, Orsay, France
info:eu-repo/semantics/restrictedAccess
fluorine-18
radiosynthesis
DPA-C5yne
DPA-714
TSPO 18 kDa
PBR
<p>DPA-C5yne, the lead compound of a novel series of DPA-714 derivatives in which the fluoroethoxy chain linked to the phenylpyrazolopyrimidine scaffold has been replaced by a fluoroalkyn-1-yl moiety, is a high affinity (Ki: 0.35 nM) and selective ligand targeting the translocator protein 18 kDa. In the present work, DPA-C5yne was labelled with no-carrier-added [18F] fluoride based on a one-step tosyloxy-for-fluorine nucleophilic substitution reaction, purified by cartridge and HPLC, and formulated as an i.v. injectable solution using a TRACERLab FX N Pro synthesizer. Typically, 4.3–5.2GBq of [18F]DPA-C5yne, ready-to-use, chemically and radiochemically pure (> 95%), was obtained with specific radioactivities ranging from 55 to 110GBq/μmol within 50–60 min, starting from a 30GBq [18F]fluoride batch (14–17%). LogP and LogD of [18F]DPA-C5yne were measured using the shake-flask method and values of 2.39 and 2.51 were found, respectively. Autoradiography studies performed on slices of ((R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA)-lesioned rat brains showed a high target-to-background ratio (1.9 ± 0.3). Selectivity and specificity of the binding for the translocator protein was demonstrated using DPA-C5yne (unlabelled), PK11195 and Flumazenil (central benzodiazepine receptor ligand) as competitors. Furthermore, DPA-C5yne proved to be stable in plasma at 37°C for at least 90min.</p>
Zenodo
2014-04-24
info:eu-repo/semantics/article
605535
user-inmind
user-eu
award_title=Imaging of Neuroinflammation in Neurodegenerative Diseases; award_number=278850; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/278850; funder_id=00k4n6c32; funder_name=European Commission;
1579541206.55184
public
J. Label Compd. Radiopharm
57
410-418
2014-04-24