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Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.

Dickens, Alex M; Vainio, Susanne; Marjamäki, Päivi; Johansson, Jarkko; Lehtiniemi, Paula; Rokka, Johanna; Rinne, Juha; Solin, Olof; Haaparanta-Solin, Merja; Jones, Paul A; Trigg, William; Anthony, Daniel C; Airas, Laura


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  <identifier identifierType="URL">https://zenodo.org/record/8583</identifier>
  <creators>
    <creator>
      <creatorName>Dickens, Alex M</creatorName>
      <givenName>Alex M</givenName>
      <familyName>Dickens</familyName>
      <affiliation>Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland and MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Vainio, Susanne</creatorName>
      <givenName>Susanne</givenName>
      <familyName>Vainio</familyName>
      <affiliation>MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Marjamäki, Päivi</creatorName>
      <givenName>Päivi</givenName>
      <familyName>Marjamäki</familyName>
      <affiliation>MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Johansson, Jarkko</creatorName>
      <givenName>Jarkko</givenName>
      <familyName>Johansson</familyName>
      <affiliation>Turku PET Centre, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Lehtiniemi, Paula</creatorName>
      <givenName>Paula</givenName>
      <familyName>Lehtiniemi</familyName>
      <affiliation>Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Rokka, Johanna</creatorName>
      <givenName>Johanna</givenName>
      <familyName>Rokka</familyName>
      <affiliation>Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Rinne, Juha</creatorName>
      <givenName>Juha</givenName>
      <familyName>Rinne</familyName>
      <affiliation>Turku PET Centre, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Solin, Olof</creatorName>
      <givenName>Olof</givenName>
      <familyName>Solin</familyName>
      <affiliation>Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Haaparanta-Solin, Merja</creatorName>
      <givenName>Merja</givenName>
      <familyName>Haaparanta-Solin</familyName>
      <affiliation>MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland</affiliation>
    </creator>
    <creator>
      <creatorName>Jones, Paul A</creatorName>
      <givenName>Paul A</givenName>
      <familyName>Jones</familyName>
      <affiliation>GE Healthcare Ltd., Amersham, United Kingdom</affiliation>
    </creator>
    <creator>
      <creatorName>Trigg, William</creatorName>
      <givenName>William</givenName>
      <familyName>Trigg</familyName>
      <affiliation>GE Healthcare Ltd., Amersham, United Kingdom</affiliation>
    </creator>
    <creator>
      <creatorName>Anthony, Daniel C</creatorName>
      <givenName>Daniel C</givenName>
      <familyName>Anthony</familyName>
      <affiliation>Department of Pharmacology, University of Oxford, Oxford, United Kingdom</affiliation>
    </creator>
    <creator>
      <creatorName>Airas, Laura</creatorName>
      <givenName>Laura</givenName>
      <familyName>Airas</familyName>
      <affiliation>Department of Neurology, Turku University Hospital, Turku, Finland</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2014</publicationYear>
  <subjects>
    <subject>neuroinflammation</subject>
    <subject>positron emission tomography</subject>
    <subject>second-generation TSPO ligand</subject>
    <subject>brain</subject>
    <subject>astrocyte</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2014-02-10</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/8583</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.2967/jnumed.113.125625</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/inmind</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ecfunded</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/zenodo</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="info:eu-repo/semantics/closedAccess">Closed Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;It remains unclear how different translocator protein (TSPO) ligands reflect the spatial extent of astrocyte or microglial activation in various neuroinflammatory conditions. Here, we use a reproducible lipopolysaccharide (LPS)-induced model of acute central nervous system inflammation to compare the binding performance of a new TSPO ligand (18)F-GE-180 with (11)C-(R)-PK11195. Using immunohistochemistry, we also explore the ability of the TSPO ligands to detect activated microglial cells and astrocytes.&lt;/p&gt;

&lt;p&gt;METHODS: Lewis rats (n = 30) were microinjected with LPS (1 or 10 &amp;mu;g) or saline (1 &amp;mu;L) into the left striatum. The animals were imaged in vivo at 16 h after the injection using PET radiotracers (18)F-GE-180 or (11)C-(R)-PK11195 (n = 3 in each group) and were killed afterward for autoradiography of the brain. Immunohistochemical assessment of OX-42 and glial fibrillary acidic protein (GFAP) was performed to identify activated microglial cells and reactive astrocytes.&lt;/p&gt;

&lt;p&gt;RESULTS: In vivo PET imaging revealed an increase in the ipsilateral TSPO binding, compared with binding in the contralateral hemisphere, after the microinjection of 10 &amp;mu;g of LPS. No increase was observed with vehicle. By autoradiography, the TSPO radiotracer binding potential in the injected hemisphere was increased after striatal injection of 1 or 10 &amp;mu;g of LPS. However, the significant increase was observed only when using (18)F-GE-180. The area of CD11b-expressing microglial cells extended beyond that of enhanced GFAP staining and mapped more closely to the extent of (18)F-GE-180 binding than to (11)C-(R)-PK11195 binding. The signal from either PET ligand was significantly increased in regions of increased GFAP immunoreactivity and OX-42 colocalization, meaning that the presence of both activated microglia and astrocytes in a given area leads to increased binding of the TSPO radiotracers.&lt;/p&gt;

&lt;p&gt;CONCLUSION: (18)F-GE-180 is able to reveal sites of activated microglia in both gray and white matter. However, the signal is increased by the presence of activated astrocytes. Therefore, (18)F-GE-180 is a promising new fluorinated longer-half-life tracer that reveals the presence of activated microglia in a manner that is superior to (11)C-(R)-PK11195 due to the higher binding potential observed for this ligand.&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>
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