April 5, 2023 Dataset Open Access

Teodoro, Rodrigo; Gündel, Daniel; Deuther-Conrad, Winnie; Toussaint, Magali; Wenzel, Barbara; Bormans, Guy; Kopka, Klaus; Brust, Peter; Moldovan, Rares-Petru

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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Teodoro, Rodrigo</dc:creator>
  <dc:creator>Gündel, Daniel</dc:creator>
  <dc:creator>Deuther-Conrad, Winnie</dc:creator>
  <dc:creator>Toussaint, Magali</dc:creator>
  <dc:creator>Wenzel, Barbara</dc:creator>
  <dc:creator>Bormans, Guy</dc:creator>
  <dc:creator>Kopka, Klaus</dc:creator>
  <dc:creator>Brust, Peter</dc:creator>
  <dc:creator>Moldovan, Rares-Petru</dc:creator>
  <dc:date>2023-04-05</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://rodare.hzdr.de/record/2252</dc:identifier>
  <dc:identifier>10.14278/rodare.2252</dc:identifier>
  <dc:identifier>oai:rodare.hzdr.de:2252</dc:identifier>
  <dc:relation>url:https://www.hzdr.de/publications/Publ-36778</dc:relation>
  <dc:relation>url:https://www.hzdr.de/publications/Publ-35005</dc:relation>
  <dc:relation>doi:10.14278/rodare.2251</dc:relation>
  <dc:relation>url:https://rodare.hzdr.de/communities/rodare</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>https://creativecommons.org/licenses/by/4.0/legalcode</dc:rights>
  <dc:subject>cannabinoid receptor type 2</dc:subject>
  <dc:subject>indole-2-carboxamide</dc:subject>
  <dc:subject>binding affinity</dc:subject>
  <dc:subject>radiochemistry</dc:subject>
  <dc:subject>fluorine-18 labeling</dc:subject>
  <dc:subject>positron-emission tomography</dc:subject>
  <dc: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</dc:title>
  <dc:type>info:eu-repo/semantics/other</dc:type>
  <dc:type>dataset</dc:type>
</oai_dc:dc>