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
DataCite XML Export
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<identifier identifierType="DOI">10.14278/rodare.1381</identifier>
<creators>
<creator>
<creatorName>Moldovan, Rares-Petru</creatorName>
<givenName>Rares-Petru</givenName>
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<creatorName>Gündel, Daniel</creatorName>
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<creatorName>Deuther-Conrad, Winnie</creatorName>
<givenName>Winnie</givenName>
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<givenName>Lea</givenName>
<familyName>Ueberham</familyName>
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<creatorName>Kaur, Sarandeep</creatorName>
<givenName>Sarandeep</givenName>
<familyName>Kaur</familyName>
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<creatorName>Otikova, Elina</creatorName>
<givenName>Elina</givenName>
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<creatorName>Teodoro, Rodrigo</creatorName>
<givenName>Rodrigo</givenName>
<familyName>Teodoro</familyName>
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<creator>
<creatorName>Lai, Thu Hang</creatorName>
<givenName>Thu Hang</givenName>
<familyName>Lai</familyName>
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<creatorName>Clauß, Oliver</creatorName>
<givenName>Oliver</givenName>
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<creator>
<creatorName>Scheunemann, Matthias</creatorName>
<givenName>Matthias</givenName>
<familyName>Scheunemann</familyName>
<affiliation>HZDR</affiliation>
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<creator>
<creatorName>Bormans, Guy</creatorName>
<givenName>Guy</givenName>
<familyName>Bormans</familyName>
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<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>
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<creator>
<creatorName>Bachmann, Michael</creatorName>
<givenName>Michael</givenName>
<familyName>Bachmann</familyName>
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<affiliation>HZDR</affiliation>
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<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>
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<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>
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<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"><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></description>
</descriptions>
</resource>
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|---|---|---|
| Views | 726 | 726 |
| Downloads | 303 | 303 |
| Data volume | 48.4 MB | 48.4 MB |
| Unique views | 291 | 291 |
| Unique downloads | 58 | 58 |
- Publication date:
- August 9, 2022
- DOI:
-
- Keyword(s):
- cannabinoid receptor type 2 naphthyrid-2-one binding affinity
- Related identifiers:
- Identical to:
https://www.hzdr.de/publications/Publ-34030 - Referenced by:
https://www.hzdr.de/publications/Publ-33987 - Communities:
- License (for files):
- Creative Commons Attribution 4.0 International