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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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{
  "DOI": "10.1002/jlcr.3252", 
  "container_title": "J Labelled Comp Radiopharm.", 
  "title": "Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714", 
  "issued": {
    "date-parts": [
      [
        2015, 
        1, 
        23
      ]
    ]
  }, 
  "abstract": "<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>", 
  "author": [
    {
      "given": "Annelaure", 
      "family": "Damont"
    }, 
    {
      "given": "S\u00e9bastien", 
      "family": "Garcia-Argote"
    }, 
    {
      "given": "David-Alexandre", 
      "family": "Buisson"
    }, 
    {
      "given": "Bernard", 
      "family": "Rousseau"
    }, 
    {
      "given": "Fr\u00e9d\u00e9ric", 
      "family": "Doll\u00e9"
    }
  ], 
  "page": "1-6", 
  "volume": "58", 
  "type": "article-journal", 
  "issue": "1", 
  "id": "14848"
}
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