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Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714

Damont, Annelaure; Garcia-Argote, Sébastien; Buisson, David-Alexandre; Rousseau, Bernard; Dollé, Frédéric


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{
  "description": "<p>DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) is a recently&nbsp;discovered fluorinated ligand of the translocator protein 18 kDa (TSPO). Labelled with the short-lived positron emitter&nbsp;fluorine-18, this structure is today the radioligand of reference for in vivo imaging of microglia activation and&nbsp;neuroinflammatory processes with positron emission tomography. In the present work, an isotopically tritium-labelled&nbsp;version was developed ([3H]DPA-714), in order to access high resolution in vitro and ex vivo microscopic autoradiography&nbsp;studies, repeated and long-lasting receptor binding studies and in vivo pharmacokinetic determination at late time points.&nbsp;Briefly, DPA-714 as reference, and its 3,5-dibrominated derivative as precursor for labelling, were both prepared from DPA-713 in nonoptimized 32% (two steps) and 10% (three steps) yields, respectively. Reductive debromination using deuterium&nbsp;gas and Pd/C as catalyst in methanol, performed at the micromolar scale, confirmed the regioselective introduction of two&nbsp;deuterium atoms at the meta positions of the phenyl ring. Tritiodebromination was analogously performed using no-carrier&nbsp;tritium gas. HPLC purification provided &gt;96% radiochemically pure [3H]DPA-714 (7 GBq) with a 2.1 TBq/mmol specific&nbsp;radioactivity. Interestingly, additional hydrogen-for-tritium exchanges were also observed at the 5-methyl and 7-methyl&nbsp;positions of the pyrazolo[1,5-a]pyrimidine, opening novel perspectives in the labelling of compounds featuring this&nbsp;heterocyclic core.</p>", 
  "creator": [
    {
      "affiliation": "CEA, DSV/I2BM, Service Hospitalier Fr\u00e9d\u00e9ric Joliot, 91401 Orsay, France", 
      "@type": "Person", 
      "name": "Damont, Annelaure"
    }, 
    {
      "affiliation": "CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France", 
      "@type": "Person", 
      "name": "Garcia-Argote, S\u00e9bastien"
    }, 
    {
      "affiliation": "CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France", 
      "@type": "Person", 
      "name": "Buisson, David-Alexandre"
    }, 
    {
      "affiliation": "CEA, DSV/iBiTec-S, Service de Chimie bioorganique et de Marquage, 91191 Gif-sur-Yvette, France", 
      "@type": "Person", 
      "name": "Rousseau, Bernard"
    }, 
    {
      "affiliation": "CEA, DSV/I2BM, Service Hospitalier Fr\u00e9d\u00e9ric Joliot, 91401 Orsay, France", 
      "@type": "Person", 
      "name": "Doll\u00e9, Fr\u00e9d\u00e9ric"
    }
  ], 
  "headline": "Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714", 
  "image": "https://zenodo.org/static/img/logos/zenodo-gradient-round.svg", 
  "datePublished": "2015-01-23", 
  "url": "https://zenodo.org/record/14848", 
  "keywords": [
    "isotopic labelling", 
    "tritium", 
    "DPA-714", 
    "TSPO 18 kDa", 
    "PBR", 
    "tritiodebromination", 
    "hydrogen-for-tritium exchange"
  ], 
  "@context": "https://schema.org/", 
  "identifier": "https://doi.org/10.1002/jlcr.3252", 
  "@id": "https://doi.org/10.1002/jlcr.3252", 
  "@type": "ScholarlyArticle", 
  "name": "Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714"
}
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