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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{
  "type": "dataset", 
  "id": "2252", 
  "DOI": "10.14278/rodare.2252", 
  "author": [
    {
      "family": "Teodoro, Rodrigo"
    }, 
    {
      "family": "G\u00fcndel, Daniel"
    }, 
    {
      "family": "Deuther-Conrad, Winnie"
    }, 
    {
      "family": "Toussaint, Magali"
    }, 
    {
      "family": "Wenzel, Barbara"
    }, 
    {
      "family": "Bormans, Guy"
    }, 
    {
      "family": "Kopka, Klaus"
    }, 
    {
      "family": "Brust, Peter"
    }, 
    {
      "family": "Moldovan, Rares-Petru"
    }
  ], 
  "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>", 
  "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", 
  "publisher": "Rodare", 
  "issued": {
    "date-parts": [
      [
        2023, 
        4, 
        5
      ]
    ]
  }
}