Journal article Open Access

Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation.

Janssen, Bieneke; Vugts, Danielle J; Wilkinson, Shane M; Ory, Dieter; Chalon, Sylvie; Hoozemans, Jeroen JM; Schuit, Robert C; Beaino, Wissam; Kooijman, Esther JM; van den Hoek, Johan; Chishty, Mansoor; Doméné, Aurélie; Van der Perren, Anke; Villa, Alessandro; Maggi, Adriana; Molenaar, Ger T; Funke, Uta; Shevchenko, Rostislav V; Baekelandt, Veerle; Bormans, Guy; Lammertsma, Adriaan A; Kassiou, Michael; Windhorst, Albert D


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      <creatorName>Janssen, Bieneke</creatorName>
      <givenName>Bieneke</givenName>
      <familyName>Janssen</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-9573-8558</nameIdentifier>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Vugts, Danielle J</creatorName>
      <givenName>Danielle J</givenName>
      <familyName>Vugts</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Wilkinson, Shane M</creatorName>
      <givenName>Shane M</givenName>
      <familyName>Wilkinson</familyName>
      <affiliation>School of Chemistry, University of Sydney, Sydney, Australia.</affiliation>
    </creator>
    <creator>
      <creatorName>Ory, Dieter</creatorName>
      <givenName>Dieter</givenName>
      <familyName>Ory</familyName>
      <affiliation>Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.</affiliation>
    </creator>
    <creator>
      <creatorName>Chalon, Sylvie</creatorName>
      <givenName>Sylvie</givenName>
      <familyName>Chalon</familyName>
      <affiliation>UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.</affiliation>
    </creator>
    <creator>
      <creatorName>Hoozemans, Jeroen JM</creatorName>
      <givenName>Jeroen JM</givenName>
      <familyName>Hoozemans</familyName>
      <affiliation>Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Schuit, Robert C</creatorName>
      <givenName>Robert C</givenName>
      <familyName>Schuit</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Beaino, Wissam</creatorName>
      <givenName>Wissam</givenName>
      <familyName>Beaino</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Kooijman, Esther JM</creatorName>
      <givenName>Esther JM</givenName>
      <familyName>Kooijman</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>van den Hoek, Johan</creatorName>
      <givenName>Johan</givenName>
      <familyName>van den Hoek</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Chishty, Mansoor</creatorName>
      <givenName>Mansoor</givenName>
      <familyName>Chishty</familyName>
      <affiliation>Pharmidex Pharmaceutical Services Ltd., London, United Kingdom.</affiliation>
    </creator>
    <creator>
      <creatorName>Doméné, Aurélie</creatorName>
      <givenName>Aurélie</givenName>
      <familyName>Doméné</familyName>
      <affiliation>UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.</affiliation>
    </creator>
    <creator>
      <creatorName>Van der Perren, Anke</creatorName>
      <givenName>Anke</givenName>
      <familyName>Van der Perren</familyName>
      <affiliation>Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium.</affiliation>
    </creator>
    <creator>
      <creatorName>Villa, Alessandro</creatorName>
      <givenName>Alessandro</givenName>
      <familyName>Villa</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-7445-916X</nameIdentifier>
      <affiliation>Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Maggi, Adriana</creatorName>
      <givenName>Adriana</givenName>
      <familyName>Maggi</familyName>
      <affiliation>Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Molenaar, Ger T</creatorName>
      <givenName>Ger T</givenName>
      <familyName>Molenaar</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands and BV Cyclotron VU, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Funke, Uta</creatorName>
      <givenName>Uta</givenName>
      <familyName>Funke</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium and BV Cyclotron VU, Amsterdam, The Netherlands.</affiliation>
    </creator>
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      <creatorName>Shevchenko, Rostislav V</creatorName>
      <givenName>Rostislav V</givenName>
      <familyName>Shevchenko</familyName>
      <affiliation>Pharmidex Pharmaceutical Services Ltd., London, United Kingdom.</affiliation>
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    <creator>
      <creatorName>Baekelandt, Veerle</creatorName>
      <givenName>Veerle</givenName>
      <familyName>Baekelandt</familyName>
      <affiliation>Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium.</affiliation>
    </creator>
    <creator>
      <creatorName>Bormans, Guy</creatorName>
      <givenName>Guy</givenName>
      <familyName>Bormans</familyName>
      <affiliation>Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.</affiliation>
    </creator>
    <creator>
      <creatorName>Lammertsma, Adriaan A</creatorName>
      <givenName>Adriaan A</givenName>
      <familyName>Lammertsma</familyName>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
    <creator>
      <creatorName>Kassiou, Michael</creatorName>
      <givenName>Michael</givenName>
      <familyName>Kassiou</familyName>
      <affiliation>School of Chemistry, University of Sydney, Sydney, Australia.</affiliation>
    </creator>
    <creator>
      <creatorName>Windhorst, Albert D</creatorName>
      <givenName>Albert D</givenName>
      <familyName>Windhorst</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-1250-7656</nameIdentifier>
      <affiliation>Department of Radiology &amp; Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation.</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2018</publicationYear>
  <dates>
    <date dateType="Issued">2018-04-26</date>
  </dates>
  <language>en</language>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/1298620</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1038/s41598-018-24814-0</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/fp7-bmc</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/inmind</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;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;The P2X&lt;sub&gt;7&lt;/sub&gt; receptor plays a significant role in microglial activation, and as a potential drug target, the P2X&lt;sub&gt;7&lt;/sub&gt; receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X&lt;sub&gt;7&lt;/sub&gt; receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X&lt;sub&gt;7&lt;/sub&gt; receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain. [&lt;sup&gt;11&lt;/sup&gt;C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X&lt;sub&gt;7&lt;/sub&gt; receptor in vivo in a hP2X&lt;sub&gt;7&lt;/sub&gt; receptor overexpressing rat model. Although no significant difference in binding of [&lt;sup&gt;11&lt;/sup&gt;C]SMW139 was observed between post mortem brain tissue of Alzheimer&amp;#39;s disease patients and that of healthy controls in in vitro autoradiography experiments, [&lt;sup&gt;11&lt;/sup&gt;C]SMW139 could be a promising tracer for P2X&lt;sub&gt;7&lt;/sub&gt; receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X&lt;sub&gt;7&lt;/sub&gt; receptor overexpressing rat model. However, further investigation of both P2X&lt;sub&gt;7&lt;/sub&gt; receptor expression and binding of [&lt;sup&gt;11&lt;/sup&gt;C]SMW139 in other neurological diseases involving microglial activation is warranted.&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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