Dataset Open Access
Teodoro, Rodrigo; Gündel, Daniel; Deuther-Conrad, Winnie; Toussaint, Magali; Wenzel, Barbara; Bormans, Guy; Kopka, Klaus; Brust, Peter; Moldovan, Rares-Petru
<?xml version='1.0' encoding='utf-8'?> <resource xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://datacite.org/schema/kernel-4" xsi:schemaLocation="http://datacite.org/schema/kernel-4 http://schema.datacite.org/meta/kernel-4.1/metadata.xsd"> <identifier identifierType="DOI">10.14278/rodare.2252</identifier> <creators> <creator> <creatorName>Teodoro, Rodrigo</creatorName> <givenName>Rodrigo</givenName> <familyName>Teodoro</familyName> <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-1425-0567</nameIdentifier> </creator> <creator> <creatorName>Gündel, Daniel</creatorName> <givenName>Daniel</givenName> <familyName>Gündel</familyName> <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-9743-2325</nameIdentifier> </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> </creator> <creator> <creatorName>Toussaint, Magali</creatorName> <givenName>Magali</givenName> <familyName>Toussaint</familyName> <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-1136-3857</nameIdentifier> </creator> <creator> <creatorName>Wenzel, Barbara</creatorName> <givenName>Barbara</givenName> <familyName>Wenzel</familyName> <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-7390-3575</nameIdentifier> </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> </creator> <creator> <creatorName>Brust, Peter</creatorName> <givenName>Peter</givenName> <familyName>Brust</familyName> <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-5555-7058</nameIdentifier> </creator> <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> </creator> </creators> <titles> <title>Data publication: Enantioselective Synthesis, Structure Activity Relationship, Radiofluorination and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET</title> </titles> <publisher>Rodare</publisher> <publicationYear>2023</publicationYear> <subjects> <subject>cannabinoid receptor type 2</subject> <subject>indole-2-carboxamide</subject> <subject>binding affinity</subject> <subject>radiochemistry</subject> <subject>fluorine-18 labeling</subject> <subject>positron-emission tomography</subject> </subjects> <dates> <date dateType="Issued">2023-04-05</date> </dates> <resourceType resourceTypeGeneral="Dataset"/> <alternateIdentifiers> <alternateIdentifier alternateIdentifierType="url">https://rodare.hzdr.de/record/2252</alternateIdentifier> </alternateIdentifiers> <relatedIdentifiers> <relatedIdentifier relatedIdentifierType="URL" relationType="IsIdenticalTo">https://www.hzdr.de/publications/Publ-36778</relatedIdentifier> <relatedIdentifier relatedIdentifierType="URL" relationType="IsReferencedBy">https://www.hzdr.de/publications/Publ-35005</relatedIdentifier> <relatedIdentifier relatedIdentifierType="DOI" relationType="IsVersionOf">10.14278/rodare.2251</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 development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation in various pathological conditions, such as neuroinflammation and cancer. Herein we report on the enantioselective synthesis of a series of highly affine fluorinated indole-2-carboxamide ligands targeting the CB2R in the brain. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (Ki = 2.1 nM) and pronounced selectivity over CB1R (factor &gt; 300). A fully automated copper-mediated radiofluorination of [18F]RM365 was established starting from the corresponding aryl boronic acid pinacol ester precursor. Preliminary in vitro evaluation of [18F]RM365 indicated species differences in the binding to CB2R (KD of 2.32 nM for the human CB2R vs. KD &gt; 10000 nM for the rat CB2R). Metabolism studies in mice revealed high stability of [18F]RM365 with fractions of parent compound of &gt; 90% in the brain and &gt; 54% in the plasma at 30 min p.i. PET imaging in a rat model of local hCB2R(D80N) overexpression in the brain demonstrate the ability of [18F]RM365 to reach and selectively label the intracranial expressed hCB2R(D80N) with high signal-to-background ratio. Thus, [18F]RM365 is a very promising PET radioligand for the imaging of upregulated hCB2R expression under pathological conditions with high potential towards clinical application in humans.</p></description> </descriptions> </resource>
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