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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluation of the PBR/TSPO radioligand [<sup>18</sup>F]DPA-714 in a rat model of focal cerebral ischemia</title><author><name sortKey="Martin, Abraham" sort="Martin, Abraham" uniqKey="Martin A" first="Abraham" last="Martín">Abraham Martín</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Boisgard, Raphael" sort="Boisgard, Raphael" uniqKey="Boisgard R" first="Raphaël" last="Boisgard">Raphaël Boisgard</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Theze, Benoit" sort="Theze, Benoit" uniqKey="Theze B" first="Benoit" last="Thézé">Benoit Thézé</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Van Camp, Nadja" sort="Van Camp, Nadja" uniqKey="Van Camp N" first="Nadja" last="Van Camp">Nadja Van Camp</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kuhnast, Bertrand" sort="Kuhnast, Bertrand" uniqKey="Kuhnast B" first="Bertrand" last="Kuhnast">Bertrand Kuhnast</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Damont, Annelaure" sort="Damont, Annelaure" uniqKey="Damont A" first="Annelaure" last="Damont">Annelaure Damont</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kassiou, Michael" sort="Kassiou, Michael" uniqKey="Kassiou M" first="Michael" last="Kassiou">Michael Kassiou</name><affiliation><nlm:aff id="aff3"><institution>University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Discipline of Medical Radiation Sciences, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>School of Chemistry, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dolle, Frederic" sort="Dolle, Frederic" uniqKey="Dolle F" first="Frédéric" last="Dollé">Frédéric Dollé</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Tavitian, Bertrand" sort="Tavitian, Bertrand" uniqKey="Tavitian B" first="Bertrand" last="Tavitian">Bertrand Tavitian</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19794397</idno><idno type="pmc">2949091</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949091</idno><idno type="RBID">PMC:2949091</idno><idno type="doi">10.1038/jcbfm.2009.205</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000071</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000071</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Evaluation of the PBR/TSPO radioligand [<sup>18</sup>F]DPA-714 in a rat model of focal cerebral ischemia</title><author><name sortKey="Martin, Abraham" sort="Martin, Abraham" uniqKey="Martin A" first="Abraham" last="Martín">Abraham Martín</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Boisgard, Raphael" sort="Boisgard, Raphael" uniqKey="Boisgard R" first="Raphaël" last="Boisgard">Raphaël Boisgard</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Theze, Benoit" sort="Theze, Benoit" uniqKey="Theze B" first="Benoit" last="Thézé">Benoit Thézé</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Van Camp, Nadja" sort="Van Camp, Nadja" uniqKey="Van Camp N" first="Nadja" last="Van Camp">Nadja Van Camp</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kuhnast, Bertrand" sort="Kuhnast, Bertrand" uniqKey="Kuhnast B" first="Bertrand" last="Kuhnast">Bertrand Kuhnast</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Damont, Annelaure" sort="Damont, Annelaure" uniqKey="Damont A" first="Annelaure" last="Damont">Annelaure Damont</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kassiou, Michael" sort="Kassiou, Michael" uniqKey="Kassiou M" first="Michael" last="Kassiou">Michael Kassiou</name><affiliation><nlm:aff id="aff3"><institution>University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Discipline of Medical Radiation Sciences, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>School of Chemistry, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dolle, Frederic" sort="Dolle, Frederic" uniqKey="Dolle F" first="Frédéric" last="Dollé">Frédéric Dollé</name><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Tavitian, Bertrand" sort="Tavitian, Bertrand" uniqKey="Tavitian B" first="Bertrand" last="Tavitian">Bertrand Tavitian</name><affiliation><nlm:aff id="aff1"><institution>INSERM U803</institution>, Orsay,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism</title><idno type="ISSN">0271-678X</idno><idno type="eISSN">1559-7016</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed <italic>in vivo</italic> PET imaging with [<sup>18</sup>F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. <italic>In vivo</italic> PET imaging showed significant increase in DPA (<italic>N,N</italic>-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. <italic>In vitro</italic> autoradiography confirmed these <italic>in vivo</italic> results. <italic>In vivo</italic> and <italic>in vitro</italic> [<sup>18</sup>F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [<sup>18</sup>F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Cereb Blood Flow Metab</journal-id><journal-title-group><journal-title>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism</journal-title></journal-title-group><issn pub-type="ppub">0271-678X</issn><issn pub-type="epub">1559-7016</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19794397</article-id><article-id pub-id-type="pmc">2949091</article-id><article-id pub-id-type="pii">jcbfm2009205</article-id><article-id pub-id-type="doi">10.1038/jcbfm.2009.205</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Evaluation of the PBR/TSPO radioligand [<sup>18</sup>F]DPA-714 in a rat model of focal cerebral ischemia</article-title><alt-title alt-title-type="running">[<sup>18</sup>F]DPA-714 in experimental cerebral ischemia</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Martín</surname><given-names>Abraham</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Boisgard</surname><given-names>Raphaël</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Thézé</surname><given-names>Benoit</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Van Camp</surname><given-names>Nadja</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kuhnast</surname><given-names>Bertrand</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Damont</surname><given-names>Annelaure</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kassiou</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Dollé</surname><given-names>Frédéric</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tavitian</surname><given-names>Bertrand</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>INSERM U803</institution>, Orsay,<country>France</country></aff><aff id="aff2"><label>2</label><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, Orsay,<country>France</country></aff><aff id="aff3"><label>3</label><institution>University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></aff><aff id="aff4"><label>4</label><institution>Discipline of Medical Radiation Sciences, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></aff><aff id="aff5"><label>5</label><institution>School of Chemistry, University of Sydney</institution>, Sydney, New South Wales,<country>Australia</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale</institution>, INSERM U803, 4, Place Géneral Leclerc, Orsay Cedex 91406, <country>France</country>. E-mail: <email>bertrand.tavitian@cea.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>01</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>30</day><month>09</month><year>2009</year></pub-date><volume>30</volume><issue>1</issue><fpage>230</fpage><lpage>241</lpage><history><date date-type="received"><day>25</day><month>05</month><year>2009</year></date><date date-type="rev-recd"><day>02</day><month>09</month><year>2009</year></date><date date-type="accepted"><day>06</day><month>09</month><year>2009</year></date></history><permissions><copyright-statement>Copyright © 2010 Nature Publishing Group</copyright-statement><copyright-year>2010</copyright-year><copyright-holder>Nature Publishing Group</copyright-holder></permissions><abstract><p>Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed <italic>in vivo</italic> PET imaging with [<sup>18</sup>F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. <italic>In vivo</italic> PET imaging showed significant increase in DPA (<italic>N,N</italic>-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. <italic>In vitro</italic> autoradiography confirmed these <italic>in vivo</italic> results. <italic>In vivo</italic> and <italic>in vitro</italic> [<sup>18</sup>F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [<sup>18</sup>F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.</p></abstract><kwd-group><kwd>cerebral ischemia</kwd><kwd>inflammatory reaction</kwd><kwd>peripheral-type benzodiazepine receptor</kwd><kwd>PET imaging</kwd><kwd>transient middle cerebral artery occlusion</kwd><kwd>TSPO</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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