Dataset Open Access
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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rdf:about="https://doi.org/10.14278/rodare.1381"> <rdf:type rdf:resource="http://www.w3.org/ns/dcat#Dataset"/> <dct:type rdf:resource="http://purl.org/dc/dcmitype/Dataset"/> <dct:identifier rdf:datatype="http://www.w3.org/2001/XMLSchema#anyURI">https://doi.org/10.14278/rodare.1381</dct:identifier> <foaf:page rdf:resource="https://doi.org/10.14278/rodare.1381"/> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0003-3119-7945"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Moldovan, Rares-Petru</foaf:name> <foaf:givenName>Rares-Petru</foaf:givenName> <foaf:familyName>Moldovan</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0001-9743-2325"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Gündel, Daniel</foaf:name> <foaf:givenName>Daniel</foaf:givenName> <foaf:familyName>Gündel</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0003-3168-3062"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Deuther-Conrad, Winnie</foaf:name> <foaf:givenName>Winnie</foaf:givenName> <foaf:familyName>Deuther-Conrad</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Ueberham, Lea</foaf:name> <foaf:givenName>Lea</foaf:givenName> <foaf:familyName>Ueberham</foaf:familyName> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Kaur, Sarandeep</foaf:name> <foaf:givenName>Sarandeep</foaf:givenName> <foaf:familyName>Kaur</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Otikova, Elina</foaf:name> <foaf:givenName>Elina</foaf:givenName> <foaf:familyName>Otikova</foaf:familyName> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0002-1425-0567"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Teodoro, Rodrigo</foaf:name> <foaf:givenName>Rodrigo</foaf:givenName> <foaf:familyName>Teodoro</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0001-8157-8979"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Lai, Thu Hang</foaf:name> <foaf:givenName>Thu Hang</foaf:givenName> <foaf:familyName>Lai</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0001-5067-4845"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Clauß, Oliver</foaf:name> <foaf:givenName>Oliver</foaf:givenName> <foaf:familyName>Clauß</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Scheunemann, Matthias</foaf:name> <foaf:givenName>Matthias</foaf:givenName> <foaf:familyName>Scheunemann</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Bormans, Guy</foaf:name> <foaf:givenName>Guy</foaf:givenName> <foaf:familyName>Bormans</foaf:familyName> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0003-4846-1271"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Kopka, Klaus</foaf:name> <foaf:givenName>Klaus</foaf:givenName> <foaf:familyName>Kopka</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0002-8029-5755"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Bachmann, Michael</foaf:name> <foaf:givenName>Michael</foaf:givenName> <foaf:familyName>Bachmann</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description rdf:about="http://orcid.org/0000-0001-5555-7058"> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Brust, Peter</foaf:name> <foaf:givenName>Peter</foaf:givenName> <foaf:familyName>Brust</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>HZDR</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:title>Data Publication: Structure-Based Design, Optimization and Development of [18F]LU13, a novel radioligand for CB2R Imaging in the Brain with PET</dct:title> <dct:publisher> <foaf:Agent> <foaf:name>Rodare</foaf:name> </foaf:Agent> </dct:publisher> <dct:issued rdf:datatype="http://www.w3.org/2001/XMLSchema#gYear">2022</dct:issued> <dcat:keyword>cannabinoid receptor type 2</dcat:keyword> <dcat:keyword>naphthyrid-2-one</dcat:keyword> <dcat:keyword>binding affinity</dcat:keyword> <dct:issued rdf:datatype="http://www.w3.org/2001/XMLSchema#date">2022-08-09</dct:issued> <owl:sameAs rdf:resource="https://rodare.hzdr.de/record/1381"/> <adms:identifier> <adms:Identifier> <skos:notation rdf:datatype="http://www.w3.org/2001/XMLSchema#anyURI">https://rodare.hzdr.de/record/1381</skos:notation> </adms:Identifier> </adms:identifier> <owl:sameAs rdf:resource="https://www.hzdr.de/publications/Publ-34030"/> <dct:isReferencedBy rdf:resource="https://www.hzdr.de/publications/Publ-33987"/> <dct:isVersionOf rdf:resource="https://doi.org/10.14278/rodare.1380"/> <dct:isPartOf rdf:resource="https://rodare.hzdr.de/communities/health"/> <dct:isPartOf rdf:resource="https://rodare.hzdr.de/communities/rodare"/> <dct:description><p>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 (<strong>[<sup>18</sup>F]5</strong>). In this study we aimed at the development of a novel <sup>18</sup>F-labeled CB2R radioligand with improved binding properties and metabolic stability. Starting from the structure of <strong>5</strong>, we developed a novel series of fluorinated derivatives by modifying the substituents at the naphthyrid-2-one subunit. Compound <strong>28</strong> (<strong>LU13</strong>) was identified with the highest binding affinity and selectivity versus CB1R (CB2R<em>K</em><sub>i</sub> = 0.6 nM; CB1R<em>K</em><sub>i</sub>/CB2R<em>K</em><sub>i</sub> &gt; 1000) and was selected for radiolabeling with <sup>18</sup>F and biological characterization. The radiofluorination was performed starting from the corresponding bromo-precursor (<strong>31</strong>) bearing a fully deuterated <em>N</em>-alkyl chain to protect against defluorination. The in vitro evaluation of <strong>[<sup>18</sup>F]LU13 </strong>proved the high binding affinity of the radioligand towards rat (rCB2R<em>K</em><sub>D</sub> = 0.2 nM) and human (hCB2R<em>K</em><sub>D</sub> = 1.1 nM) CB2R. Metabolism studies in mice revealed a metabolic stability at 30 min p.i. with fractions of parent compound of &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 <strong>[<sup>18</sup>F]LU13</strong> to reach and selectively label the hCB2R in the brain. Thus, <strong>[<sup>18</sup>F]LU13 </strong>is a novel and highly promising PET radioligand for the imaging of up regulated CB2R expression under pathological conditions in the brain.</p></dct:description> <dct:accessRights rdf:resource="http://publications.europa.eu/resource/authority/access-right/PUBLIC"/> <dct:accessRights> <dct:RightsStatement rdf:about="info:eu-repo/semantics/openAccess"> <rdfs:label>Open Access</rdfs:label> </dct:RightsStatement> </dct:accessRights> <dcat:distribution> <dcat:Distribution> <dct:rights> <dct:RightsStatement rdf:about="https://creativecommons.org/licenses/by/4.0/legalcode"> <rdfs:label>Creative Commons Attribution 4.0 International</rdfs:label> </dct:RightsStatement> </dct:rights> <dcat:accessURL rdf:resource="https://doi.org/10.14278/rodare.1381"/> </dcat:Distribution> </dcat:distribution> </rdf:Description> </rdf:RDF>
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