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Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714

Damont, Annelaure; Garcia-Argote, Sébastien; Buisson, David-Alexandre; Rousseau, Bernard; Dollé, Frédéric


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  <identifier identifierType="URL">https://zenodo.org/record/14848</identifier>
  <creators>
    <creator>
      <creatorName>Damont, Annelaure</creatorName>
      <givenName>Annelaure</givenName>
      <familyName>Damont</familyName>
      <affiliation>CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, 91401 Orsay, France</affiliation>
    </creator>
    <creator>
      <creatorName>Garcia-Argote, Sébastien</creatorName>
      <givenName>Sébastien</givenName>
      <familyName>Garcia-Argote</familyName>
      <affiliation>CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France</affiliation>
    </creator>
    <creator>
      <creatorName>Buisson, David-Alexandre</creatorName>
      <givenName>David-Alexandre</givenName>
      <familyName>Buisson</familyName>
      <affiliation>CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France</affiliation>
    </creator>
    <creator>
      <creatorName>Rousseau, Bernard</creatorName>
      <givenName>Bernard</givenName>
      <familyName>Rousseau</familyName>
      <affiliation>CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France</affiliation>
    </creator>
    <creator>
      <creatorName>Dollé, Frédéric</creatorName>
      <givenName>Frédéric</givenName>
      <familyName>Dollé</familyName>
      <affiliation>CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, 91401 Orsay, France</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2015</publicationYear>
  <subjects>
    <subject>isotopic labelling</subject>
    <subject>tritium</subject>
    <subject>DPA-714</subject>
    <subject>TSPO 18 kDa</subject>
    <subject>PBR</subject>
    <subject>tritiodebromination</subject>
    <subject>hydrogen-for-tritium exchange</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2015-01-23</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/14848</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1002/jlcr.3252</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="info:eu-repo/semantics/closedAccess">Closed Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) is a recently&amp;nbsp;discovered fluorinated ligand of the translocator protein 18 kDa (TSPO). Labelled with the short-lived positron emitter&amp;nbsp;fluorine-18, this structure is today the radioligand of reference for in vivo imaging of microglia activation and&amp;nbsp;neuroinflammatory processes with positron emission tomography. In the present work, an isotopically tritium-labelled&amp;nbsp;version was developed ([3H]DPA-714), in order to access high resolution in vitro and ex vivo microscopic autoradiography&amp;nbsp;studies, repeated and long-lasting receptor binding studies and in vivo pharmacokinetic determination at late time points.&amp;nbsp;Briefly, DPA-714 as reference, and its 3,5-dibrominated derivative as precursor for labelling, were both prepared from DPA-713 in nonoptimized 32% (two steps) and 10% (three steps) yields, respectively. Reductive debromination using deuterium&amp;nbsp;gas and Pd/C as catalyst in methanol, performed at the micromolar scale, confirmed the regioselective introduction of two&amp;nbsp;deuterium atoms at the meta positions of the phenyl ring. Tritiodebromination was analogously performed using no-carrier&amp;nbsp;tritium gas. HPLC purification provided &amp;gt;96% radiochemically pure [3H]DPA-714 (7 GBq) with a 2.1 TBq/mmol specific&amp;nbsp;radioactivity. Interestingly, additional hydrogen-for-tritium exchanges were also observed at the 5-methyl and 7-methyl&amp;nbsp;positions of the pyrazolo[1,5-a]pyrimidine, opening novel perspectives in the labelling of compounds featuring this&amp;nbsp;heterocyclic core.&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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