Dataset Open Access

Data Publication: Structure-Based Design, Optimization and Development of [18F]LU13, a novel radioligand for CB2R Imaging in the Brain with PET

Moldovan, Rares-Petru; Gündel, Daniel; Deuther-Conrad, Winnie; Ueberham, Lea; Kaur, Sarandeep; Otikova, Elina; Teodoro, Rodrigo; Lai, Thu Hang; Clauß, Oliver; Scheunemann, Matthias; Bormans, Guy; Kopka, Klaus; Bachmann, Michael; Brust, Peter


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  <identifier identifierType="DOI">10.14278/rodare.1381</identifier>
  <creators>
    <creator>
      <creatorName>Moldovan, Rares-Petru</creatorName>
      <givenName>Rares-Petru</givenName>
      <familyName>Moldovan</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-3119-7945</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Gündel, Daniel</creatorName>
      <givenName>Daniel</givenName>
      <familyName>Gündel</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-9743-2325</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Deuther-Conrad, Winnie</creatorName>
      <givenName>Winnie</givenName>
      <familyName>Deuther-Conrad</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-3168-3062</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Ueberham, Lea</creatorName>
      <givenName>Lea</givenName>
      <familyName>Ueberham</familyName>
    </creator>
    <creator>
      <creatorName>Kaur, Sarandeep</creatorName>
      <givenName>Sarandeep</givenName>
      <familyName>Kaur</familyName>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Otikova, Elina</creatorName>
      <givenName>Elina</givenName>
      <familyName>Otikova</familyName>
    </creator>
    <creator>
      <creatorName>Teodoro, Rodrigo</creatorName>
      <givenName>Rodrigo</givenName>
      <familyName>Teodoro</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-1425-0567</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Lai, Thu Hang</creatorName>
      <givenName>Thu Hang</givenName>
      <familyName>Lai</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-8157-8979</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Clauß, Oliver</creatorName>
      <givenName>Oliver</givenName>
      <familyName>Clauß</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-5067-4845</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Scheunemann, Matthias</creatorName>
      <givenName>Matthias</givenName>
      <familyName>Scheunemann</familyName>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Bormans, Guy</creatorName>
      <givenName>Guy</givenName>
      <familyName>Bormans</familyName>
    </creator>
    <creator>
      <creatorName>Kopka, Klaus</creatorName>
      <givenName>Klaus</givenName>
      <familyName>Kopka</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-4846-1271</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Bachmann, Michael</creatorName>
      <givenName>Michael</givenName>
      <familyName>Bachmann</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-8029-5755</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
    <creator>
      <creatorName>Brust, Peter</creatorName>
      <givenName>Peter</givenName>
      <familyName>Brust</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-5555-7058</nameIdentifier>
      <affiliation>HZDR</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Data Publication: Structure-Based Design, Optimization and Development of [18F]LU13, a novel radioligand for CB2R Imaging in the Brain with PET</title>
  </titles>
  <publisher>Rodare</publisher>
  <publicationYear>2022</publicationYear>
  <subjects>
    <subject>cannabinoid receptor type 2</subject>
    <subject>naphthyrid-2-one</subject>
    <subject>binding affinity</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2022-08-09</date>
  </dates>
  <resourceType resourceTypeGeneral="Dataset"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://rodare.hzdr.de/record/1381</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsIdenticalTo">https://www.hzdr.de/publications/Publ-34030</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsReferencedBy">https://www.hzdr.de/publications/Publ-33987</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsVersionOf">10.14278/rodare.1380</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://rodare.hzdr.de/communities/health</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://rodare.hzdr.de/communities/rodare</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://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;The cannabinoid receptor type 2 (CB2R) is an attractive target for diagnosis and therapy of neurodegenerative diseases and cancer. Recently, we reported a novel naphthyrid-2-one based positron-emission tomography (PET) radioligand for imaging of the CB2R in the brain (&lt;strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]5&lt;/strong&gt;). In this study we aimed at the development of a novel &lt;sup&gt;18&lt;/sup&gt;F-labeled CB2R radioligand with improved binding properties and metabolic stability. Starting from the structure of &lt;strong&gt;5&lt;/strong&gt;, we developed a novel series of fluorinated derivatives by modifying the substituents at the naphthyrid-2-one subunit. Compound &lt;strong&gt;28&lt;/strong&gt; (&lt;strong&gt;LU13&lt;/strong&gt;) was identified with the highest binding affinity and selectivity versus CB1R (CB2R&lt;em&gt;K&lt;/em&gt;&lt;sub&gt;i&lt;/sub&gt; = 0.6 nM; CB1R&lt;em&gt;K&lt;/em&gt;&lt;sub&gt;i&lt;/sub&gt;/CB2R&lt;em&gt;K&lt;/em&gt;&lt;sub&gt;i&lt;/sub&gt; &amp;gt; 1000) and was selected for radiolabeling with &lt;sup&gt;18&lt;/sup&gt;F and biological characterization. The radiofluorination was performed starting from the corresponding bromo-precursor (&lt;strong&gt;31&lt;/strong&gt;) bearing a fully deuterated &lt;em&gt;N&lt;/em&gt;-alkyl chain to protect against defluorination. The in vitro evaluation of &lt;strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]LU13 &lt;/strong&gt;proved the high binding affinity of the radioligand towards rat (rCB2R&lt;em&gt;K&lt;/em&gt;&lt;sub&gt;D&lt;/sub&gt; = 0.2 nM) and human (hCB2R&lt;em&gt;K&lt;/em&gt;&lt;sub&gt;D&lt;/sub&gt; = 1.1 nM) CB2R. Metabolism studies in mice revealed a metabolic stability at 30 min p.i. with fractions of parent compound of &amp;gt;80% in the brain and 90% in the spleen with only trace of defluorination products detected in plasma. PET imaging in a rat model of vector-based/related overexpression in the striatum revealed a high signal to background ratio, demonstrating the ability of &lt;strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]LU13&lt;/strong&gt; to reach and selectively label the hCB2R in the brain. Thus, &lt;strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]LU13 &lt;/strong&gt;is a novel and highly promising PET radioligand for the imaging of up regulated CB2R expression under pathological conditions in the brain.&lt;/p&gt;</description>
  </descriptions>
</resource>
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