AustralieFrV1, Main, Exploration, bibRecord, 004399

[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

Identifieur interne : 004399 ( Main/Exploration ); précédent : 004398; suivant : 004400

[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.

RBID : PMC:3572061

Abstract

Purpose

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.

Methods

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.

Results

Uptake of [¹¹C]PK11195 vs [¹⁸F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 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 [¹¹C]PK11195 or with [¹⁸F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [¹¹C]PK11195 and [¹⁸F]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 vs 4.66±2.50 for [¹¹C]PK11195 vs [¹⁸F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [¹⁸F]DPA-714.

Conclusions

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572061

DOI: 10.1371/journal.pone.0056441
PubMed: 23418569
PubMed Central: 3572061

Affiliations:

Le document en format XML

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F]DPA-714: Direct Comparison with [<sup>11</sup>
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<author><name sortKey="Boutin, Herve" sort="Boutin, Herve" uniqKey="Boutin H" first="Hervé" last="Boutin">Hervé Boutin</name>
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<author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name>
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<author><name sortKey="Julyan, Peter" sort="Julyan, Peter" uniqKey="Julyan P" first="Peter" last="Julyan">Peter Julyan</name>
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<author><name sortKey="Wilkinson, Shane M" sort="Wilkinson, Shane M" uniqKey="Wilkinson S" first="Shane M." last="Wilkinson">Shane M. Wilkinson</name>
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</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="4"><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>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
<settlement type="city">Sydney</settlement>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
</author>
<author><name sortKey="Brown, Gavin" sort="Brown, Gavin" uniqKey="Brown G" first="Gavin" last="Brown">Gavin Brown</name>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
<settlement type="city">Manchester</settlement>
</placeName>
<orgName type="university">Université de Manchester</orgName>
</affiliation>
</author>
<author><name sortKey="Herholz, Karl" sort="Herholz, Karl" uniqKey="Herholz K" first="Karl" last="Herholz">Karl Herholz</name>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
<settlement type="city">Manchester</settlement>
</placeName>
<orgName type="university">Université de Manchester</orgName>
</affiliation>
</author>
<author><name sortKey="Kassiou, Michael" sort="Kassiou, Michael" uniqKey="Kassiou M" first="Michael" last="Kassiou">Michael Kassiou</name>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
<settlement type="city">Sydney</settlement>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
<settlement type="city">Sydney</settlement>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
<settlement type="city">Sydney</settlement>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</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="4"><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>
<placeName><settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
<settlement type="city">Manchester</settlement>
</placeName>
<orgName type="university">Université de Manchester</orgName>
</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>
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</settlement>
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Serveur d'exploration sur les relations entre la France et l'Australie

[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

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	Serveur d'exploration sur les relations entre la France et l'Australie
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