[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats
Identifieur interne : 002914 ( Pmc/Curation ); précédent : 002913; suivant : 002915[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats
Auteurs : Hervé Boutin [Royaume-Uni] ; Christian Prenant [Royaume-Uni] ; Renaud Maroy [France] ; James Galea [Royaume-Uni] ; Andrew D. Greenhalgh [Royaume-Uni] ; Alison Smigova [Royaume-Uni] ; Christopher Cawthorne [Royaume-Uni] ; Peter Julyan [Royaume-Uni] ; Shane M. Wilkinson [Australie] ; Samuel D. Banister [Australie] ; Gavin Brown [Royaume-Uni] ; Karl Herholz [Royaume-Uni] ; Michael Kassiou [Australie] ; Nancy J. Rothwell [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats.
Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia.
Uptake of [11C]PK11195
In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of [18F] which facilitates distribution of the tracer across PET centre, [18F]DPA-714 is a good alternative for TSPO imaging.
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DOI: 10.1371/journal.pone.0056441
PubMed: 23418569
PubMed Central: 3572061
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Banister</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Brown, Gavin" sort="Brown, Gavin" uniqKey="Brown G" first="Gavin" last="Brown">Gavin Brown</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Herholz, Karl" sort="Herholz, Karl" uniqKey="Herholz K" first="Karl" last="Herholz">Karl Herholz</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Kassiou, Michael" sort="Kassiou, Michael" uniqKey="Kassiou M" first="Michael" last="Kassiou">Michael Kassiou</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, University of Sydney, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Discipline of Medical Radiation Sciences, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Discipline of Medical Radiation Sciences, University of Sydney, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Brain and Mind Research Institute, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Brain and Mind Research Institute, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Rothwell, Nancy J" sort="Rothwell, Nancy J" uniqKey="Rothwell N" first="Nancy J." last="Rothwell">Nancy J. Rothwell</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Life Sciences, University of Manchester, Manchester</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23418569</idno><idno type="pmc">3572061</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572061</idno><idno type="RBID">PMC:3572061</idno><idno type="doi">10.1371/journal.pone.0056441</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002A64</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002A64</idno><idno type="wicri:Area/Pmc/Curation">002914</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002914</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">[<sup>18</sup>F]DPA-714: Direct Comparison with [<sup>11</sup>C]PK11195 in a Model of Cerebral Ischemia in Rats</title><author><name sortKey="Boutin, Herve" sort="Boutin, Herve" uniqKey="Boutin H" first="Hervé" last="Boutin">Hervé Boutin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Medical and Human Sciences, University of Manchester, Manchester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Prenant, Christian" sort="Prenant, Christian" uniqKey="Prenant C" first="Christian" last="Prenant">Christian Prenant</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Maroy, Renaud" sort="Maroy, Renaud" uniqKey="Maroy R" first="Renaud" last="Maroy">Renaud Maroy</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Service Hospitalier Frédéric Joliot – Commissariat à l'Energie Atomique, Orsay, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service Hospitalier Frédéric Joliot – Commissariat à l'Energie Atomique, Orsay</wicri:regionArea></affiliation></author><author><name sortKey="Galea, James" sort="Galea, James" uniqKey="Galea J" first="James" last="Galea">James Galea</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Life Sciences, University of Manchester, Manchester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford</wicri:regionArea></affiliation></author><author><name sortKey="Greenhalgh, Andrew D" sort="Greenhalgh, Andrew D" uniqKey="Greenhalgh A" first="Andrew D." last="Greenhalgh">Andrew D. Greenhalgh</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Life Sciences, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Smigova, Alison" sort="Smigova, Alison" uniqKey="Smigova A" first="Alison" last="Smigova">Alison Smigova</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Julyan, Peter" sort="Julyan, Peter" uniqKey="Julyan P" first="Peter" last="Julyan">Peter Julyan</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>North Western Medical Physics, Christie Hospital, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>North Western Medical Physics, Christie Hospital, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Wilkinson, Shane M" sort="Wilkinson, Shane M" uniqKey="Wilkinson S" first="Shane M." last="Wilkinson">Shane M. Wilkinson</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Banister, Samuel D" sort="Banister, Samuel D" uniqKey="Banister S" first="Samuel D." last="Banister">Samuel D. Banister</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Brown, Gavin" sort="Brown, Gavin" uniqKey="Brown G" first="Gavin" last="Brown">Gavin Brown</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Herholz, Karl" sort="Herholz, Karl" uniqKey="Herholz K" first="Karl" last="Herholz">Karl Herholz</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wolfson Molecular Imaging Centre, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Kassiou, Michael" sort="Kassiou, Michael" uniqKey="Kassiou M" first="Michael" last="Kassiou">Michael Kassiou</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, University of Sydney, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Discipline of Medical Radiation Sciences, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Discipline of Medical Radiation Sciences, University of Sydney, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Brain and Mind Research Institute, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Brain and Mind Research Institute, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Rothwell, Nancy J" sort="Rothwell, Nancy J" uniqKey="Rothwell N" first="Nancy J." last="Rothwell">Nancy J. Rothwell</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Life Sciences, University of Manchester, Manchester</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [<sup>18</sup>F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [<sup>18</sup>F]DPA-714, it was compared directly to [<sup>11</sup>C]PK11195 in experimental cerebral ischaemia in rats.</p></sec><sec><title>Methods</title><p>Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [<sup>11</sup>C]PK11195 and/or [<sup>18</sup>F]DPA-714 under anaesthesia.</p></sec><sec><title>Results</title><p>Uptake of [<sup>11</sup>C]PK11195 <italic>vs</italic> [<sup>18</sup>F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 <italic>vs</italic> 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [<sup>11</sup>C]PK11195 or with [<sup>18</sup>F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [<sup>11</sup>C]PK11195 and [<sup>18</sup>F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 <italic>vs</italic> 4.66±2.50 for [<sup>11</sup>C]PK11195 <italic>vs</italic> [<sup>18</sup>F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [<sup>18</sup>F]DPA-714.</p></sec><sec><title>Conclusions</title><p>In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [<sup>18</sup>F]DPA-714 displayed a higher signal-to-noise ratio than [<sup>11</sup>C]PK11195. Our results suggest that, with the longer half-life of [<sup>18</sup>F] which facilitates distribution of the tracer across PET centre, [<sup>18</sup>F]DPA-714 is a good alternative for TSPO imaging.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lucas, Sm" uniqKey="Lucas S">SM Lucas</name></author><author><name sortKey="Rothwell, Nj" uniqKey="Rothwell N">NJ Rothwell</name></author><author><name sortKey="Gibson, Rm" uniqKey="Gibson R">RM Gibson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaftel, Ss" uniqKey="Shaftel S">SS Shaftel</name></author><author><name sortKey="Griffin, Ws" uniqKey="Griffin W">WS Griffin</name></author><author><name sortKey="O Banion, Mk" uniqKey="O Banion M">MK O'Banion</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mrak, Re" uniqKey="Mrak R">RE Mrak</name></author><author><name sortKey="Griffin, Ws" uniqKey="Griffin W">WS 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Boutin</name></author><author><name sortKey="Van, Cn" uniqKey="Van C">CN Van</name></author><author><name sortKey="Thominiaux, C" uniqKey="Thominiaux C">C Thominiaux</name></author><author><name sortKey="Hantraye, P" uniqKey="Hantraye P">P Hantraye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Damont, A" uniqKey="Damont A">A Damont</name></author><author><name sortKey="Boisgard, R" uniqKey="Boisgard R">R Boisgard</name></author><author><name sortKey="Kuhnast, B" uniqKey="Kuhnast B">B Kuhnast</name></author><author><name sortKey="Lemee, F" uniqKey="Lemee F">F Lemee</name></author><author><name sortKey="Raggiri, G" uniqKey="Raggiri G">G Raggiri</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23418569</article-id><article-id pub-id-type="pmc">3572061</article-id><article-id pub-id-type="publisher-id">PONE-D-11-25095</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0056441</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immunity</subject><subj-group><subject>Inflammation</subject></subj-group></subj-group></subj-group><subj-group><subject>Model Organisms</subject><subj-group><subject>Animal Models</subject><subj-group><subject>Rat</subject></subj-group></subj-group></subj-group><subj-group><subject>Neuroscience</subject><subj-group><subject>Neuroimaging</subject><subj-group><subject>Pet</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Neurology</subject><subj-group><subject>Cerebrovascular Diseases</subject><subj-group><subject>Ischemic Stroke</subject></subj-group></subj-group></subj-group><subj-group><subject>Radiology</subject><subj-group><subject>Nuclear Medicine</subject><subj-group><subject>PET imaging</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>[<sup>18</sup>F]DPA-714: Direct Comparison with [<sup>11</sup>C]PK11195 in a Model of Cerebral Ischemia in Rats</article-title><alt-title alt-title-type="running-head">[<sup>18</sup>F]DPA-714 - [<sup>11</sup>C]PK11195 Comparison in Stroke</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Boutin</surname><given-names>Hervé</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Prenant</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Maroy</surname><given-names>Renaud</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Galea</surname><given-names>James</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Greenhalgh</surname><given-names>Andrew D.</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¤</sup></xref></contrib><contrib contrib-type="author"><name><surname>Smigova</surname><given-names>Alison</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cawthorne</surname><given-names>Christopher</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Julyan</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wilkinson</surname><given-names>Shane M.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Banister</surname><given-names>Samuel D.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Gavin</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Herholz</surname><given-names>Karl</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kassiou</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rothwell</surname><given-names>Nancy J.</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Service Hospitalier Frédéric Joliot – Commissariat à l'Energie Atomique, Orsay, France</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom</addr-line></aff><aff id="aff6"><label>6</label><addr-line>North Western Medical Physics, Christie Hospital, Manchester, United Kingdom</addr-line></aff><aff id="aff7"><label>7</label><addr-line>School of Chemistry, University of Sydney, Sydney, Australia</addr-line></aff><aff id="aff8"><label>8</label><addr-line>Discipline of Medical Radiation Sciences, University of Sydney, Sydney, Australia</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Brain and Mind Research Institute, University of Sydney, Sydney, Australia</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Chen</surname><given-names>Chin-Tu</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>The University of Chicago, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>herve.boutin@manchester.ac.uk</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>NJR is a non-executive director of AstraZeneca plc but there was no involvement of the company in any aspect of the present study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.</p></fn><fn fn-type="con"><p>PET imaging support: AS CC. Conceived and designed the experiments: HB MK. Performed the experiments: HB CP JG ADG. Analyzed the data: HB. Contributed reagents/materials/analysis tools: RM PJ SMW SDB GB MK. Wrote the paper: HB MK KH NJR.</p></fn><fn id="fn1" fn-type="current-aff"><label>¤</label><p>Current address: Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Quebec, Canada</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>13</day><month>2</month><year>2013</year></pub-date><volume>8</volume><issue>2</issue><elocation-id>e56441</elocation-id><history><date date-type="received"><day>14</day><month>12</month><year>2011</year></date><date date-type="accepted"><day>11</day><month>1</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Boutin et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><sec><title>Purpose</title><p>Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [<sup>18</sup>F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [<sup>18</sup>F]DPA-714, it was compared directly to [<sup>11</sup>C]PK11195 in experimental cerebral ischaemia in rats.</p></sec><sec><title>Methods</title><p>Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [<sup>11</sup>C]PK11195 and/or [<sup>18</sup>F]DPA-714 under anaesthesia.</p></sec><sec><title>Results</title><p>Uptake of [<sup>11</sup>C]PK11195 <italic>vs</italic> [<sup>18</sup>F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 <italic>vs</italic> 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [<sup>11</sup>C]PK11195 or with [<sup>18</sup>F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [<sup>11</sup>C]PK11195 and [<sup>18</sup>F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 <italic>vs</italic> 4.66±2.50 for [<sup>11</sup>C]PK11195 <italic>vs</italic> [<sup>18</sup>F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [<sup>18</sup>F]DPA-714.</p></sec><sec><title>Conclusions</title><p>In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [<sup>18</sup>F]DPA-714 displayed a higher signal-to-noise ratio than [<sup>11</sup>C]PK11195. Our results suggest that, with the longer half-life of [<sup>18</sup>F] which facilitates distribution of the tracer across PET centre, [<sup>18</sup>F]DPA-714 is a good alternative for TSPO imaging.</p></sec></abstract><funding-group><funding-statement>This work was supported by the Wolfson Molecular Imaging Centre, Manchester; Prof. N. Rothwell is funded by MRC, UK; Dr H. Boutin was funded by MRC, UK and is now funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n°HEALTH-F2-2011-278850 (INMiND). The Bioimaging Facility microscopes used in this study were purchased with grants from Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust and the University of Manchester Strategic Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="9"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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