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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


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{
  "identifier": "https://doi.org/10.14278/rodare.1381", 
  "sameAs": [
    "https://www.hzdr.de/publications/Publ-34030"
  ], 
  "@context": "https://schema.org/", 
  "distribution": [
    {
      "@type": "DataDownload", 
      "fileFormat": "7z", 
      "contentUrl": "https://rodare.hzdr.de/api/files/c0642be8-16d1-43e4-a927-6732efebb237/PPT_LU13_HPLC.7z"
    }
  ], 
  "license": "https://creativecommons.org/licenses/by/4.0/legalcode", 
  "url": "https://rodare.hzdr.de/record/1381", 
  "keywords": [
    "cannabinoid receptor type 2", 
    "naphthyrid-2-one", 
    "binding affinity"
  ], 
  "name": "Data Publication: Structure-Based Design, Optimization and Development of [18F]LU13, a novel radioligand for CB2R Imaging in the Brain with PET", 
  "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>", 
  "@type": "Dataset", 
  "@id": "https://doi.org/10.14278/rodare.1381", 
  "creator": [
    {
      "name": "Moldovan, Rares-Petru", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0003-3119-7945"
    }, 
    {
      "name": "G\u00fcndel, Daniel", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0001-9743-2325"
    }, 
    {
      "name": "Deuther-Conrad, Winnie", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0003-3168-3062"
    }, 
    {
      "name": "Ueberham, Lea", 
      "@type": "Person"
    }, 
    {
      "name": "Kaur, Sarandeep", 
      "@type": "Person", 
      "affiliation": "HZDR"
    }, 
    {
      "name": "Otikova, Elina", 
      "@type": "Person"
    }, 
    {
      "name": "Teodoro, Rodrigo", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0002-1425-0567"
    }, 
    {
      "name": "Lai, Thu Hang", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0001-8157-8979"
    }, 
    {
      "name": "Clau\u00df, Oliver", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0001-5067-4845"
    }, 
    {
      "name": "Scheunemann, Matthias", 
      "@type": "Person", 
      "affiliation": "HZDR"
    }, 
    {
      "name": "Bormans, Guy", 
      "@type": "Person"
    }, 
    {
      "name": "Kopka, Klaus", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0003-4846-1271"
    }, 
    {
      "name": "Bachmann, Michael", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0002-8029-5755"
    }, 
    {
      "name": "Brust, Peter", 
      "@type": "Person", 
      "affiliation": "HZDR", 
      "@id": "https://orcid.org/0000-0001-5555-7058"
    }
  ], 
  "datePublished": "2022-08-09"
}
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