Journal article Open Access

[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.

Boutin, Hervé; Murray, Katie; Pradillo, Jesus; Maroy, Renaud; Smigova, Alison; Gerhard, Alexander; Jones, Paul A; Trigg, William


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  <identifier identifierType="URL">https://zenodo.org/record/15873</identifier>
  <creators>
    <creator>
      <creatorName>Boutin, Hervé</creatorName>
      <givenName>Hervé</givenName>
      <familyName>Boutin</familyName>
      <affiliation>Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Murray, Katie</creatorName>
      <givenName>Katie</givenName>
      <familyName>Murray</familyName>
      <affiliation>Faculty of Life Sciences, University of Manchester, Manchester, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Pradillo, Jesus</creatorName>
      <givenName>Jesus</givenName>
      <familyName>Pradillo</familyName>
      <affiliation>Faculty of Life Sciences, University of Manchester, Manchester, UK; Present address: Universidad Complutense/Politecnica de Madrid, Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Maroy, Renaud</creatorName>
      <givenName>Renaud</givenName>
      <familyName>Maroy</familyName>
      <affiliation>SHFJ - CEA Orsay, France</affiliation>
    </creator>
    <creator>
      <creatorName>Smigova, Alison</creatorName>
      <givenName>Alison</givenName>
      <familyName>Smigova</familyName>
      <affiliation>Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Gerhard, Alexander</creatorName>
      <givenName>Alexander</givenName>
      <familyName>Gerhard</familyName>
      <affiliation>Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Jones, Paul A</creatorName>
      <givenName>Paul A</givenName>
      <familyName>Jones</familyName>
      <affiliation>GE Healthcare Ltd., Amersham, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Trigg, William</creatorName>
      <givenName>William</givenName>
      <familyName>Trigg</familyName>
      <affiliation>GE Healthcare Ltd., Amersham, UK</affiliation>
    </creator>
  </creators>
  <titles>
    <title>[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2014</publicationYear>
  <subjects>
    <subject>positron emission tomography</subject>
    <subject>translocator protein</subject>
    <subject> R-PK11195</subject>
    <subject>brain ischemia</subject>
    <subject>GE-180</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2014-10-29</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/15873</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1007/s00259-014-2939-8</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/inmind</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ecfunded</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;PURPOSE: Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer 11C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer 18F-GE-180 in a rat model of stroke.&lt;/p&gt;

&lt;p&gt;METHODS: Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with 11C-R-PK11195 and 18F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP).&lt;/p&gt;

&lt;p&gt;RESULTS: 18F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of 11C-R-PK11195 uptake (1.5&amp;thinsp;&amp;plusmn;&amp;thinsp;0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BPND&amp;thinsp;=&amp;thinsp;3.5&amp;thinsp;&amp;plusmn;&amp;thinsp;0.4 and 2.4&amp;thinsp;&amp;plusmn;&amp;thinsp;0.5 for 18F-GE-180 and 11C-R-PK11195, respectively, with R 1 = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180 significantly displaced 18F-GE-180 (69&amp;thinsp;&amp;plusmn;&amp;thinsp;5 % and 63&amp;thinsp;&amp;plusmn;&amp;thinsp;4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry.&lt;/p&gt;

&lt;p&gt;CONCLUSION: The in vivo binding characteristics of 18F-GE-180 demonstrate a better signal to noise ratio than 11C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in healthy tissue. These results provide evidence that 18F-GE-180 is a strong candidate to replace 11C-R-PK11195.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/FP7/278850/">278850</awardNumber>
      <awardTitle>Imaging of Neuroinflammation in Neurodegenerative Diseases</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>
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