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@INPROCEEDINGS{Breunig:825295,
      author       = {Breunig, Katharina and Bier, Dirk and Holschbach, Marcus
                      and Schulze, Annette and Coenen, Heinrich Hubert},
      title        = {{S}ynthesis and in vitro evaluation of radiobrominated
                      adenosine {A}(1) receptor ligand [*{B}r] {CPBPX}},
      reportid     = {FZJ-2016-07759},
      year         = {2015},
      abstract     = {Objectives [18F]CPFPX
                      (8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine) [1]
                      is an established ligand for investigation of the adenosine
                      A1 receptor (A1AR) in man using PET. The iodinated
                      derivative [131I]CPIPX
                      (8-cyclopentyl-3-[(E)-3-[131I]iodoprop-2-en-1-yl]-1-propylxanthine)
                      [2] has been synthesized as well and evaluated with regard
                      to its binding profile. Since no radiobrominated A1AR ligand
                      is known so far, the synthesis of the radiobrominated
                      analogue [*Br]CPBPX
                      (8-cyclopentyl-3-[(E)-3-[*Br]bromoprop-2-en-1-yl]-1-propylxanthine)
                      was performed for closing the gap of lipophilicity in this
                      xanthine series, which is important for systematic studies.
                      Methods The applied radionuclide mixture of 76,77,82Br (*Br)
                      was produced via natSe(p,xn)-reactions on the new target
                      material NiSe at the BC1710 cyclotron of the
                      Forschungszentrum Jülich and isolated as sodium
                      [*Br]bromide in no-carrier-added form [3]. The
                      radiosynthesis of [*Br]CPBPX was carried out via
                      radiobromo-destannylation of the tributyltin precursor by in
                      situ oxidation of n.c.a. [*Br]bromide. The binding profile
                      of the new ligand to the A1AR was investigated in vitro. For
                      the determination of the logP value of [*Br]CPBPX, a new
                      experimental procedure had to be developed, as the
                      radioligand decomposes in water/octanol yielding a polar
                      compound (probably free bromide). The conventional
                      liquid-liquid extraction was followed by an additional thin
                      layer chromatography of both phases, in order to separate
                      hydrophilic from lipophilic components, and hence to allow
                      the determination of the “true” logP value. Results
                      [*Br]CPBPX was obtained after 0.5 min at RT in radiochemical
                      yields of 54 ± $8 \%$ with a molar activity of 8.6
                      GBq/µmol. The latter would be enhanced by using enriched
                      selenium as target material. In competition studies a
                      KI-value of 26 nM was determined for CPBPX (KI of CPFPX in
                      relation to [3H]DPCPX 4.9 nM). Preliminary in vitro
                      autoradiographic studies on rat brain slices show an
                      increased accumulation of [*Br]CPBPX in areas with high A1AR
                      density and a fraction of specific binding of ca. $20 \%.$
                      Using the improved experimental procedure, a logP value of
                      3.4 was determined for [*Br]CPBPX. Conclusions [*Br]CPBPX
                      closes the gap of lipophilicity of the known fluoro and iodo
                      derivatives, but its affinity to the A1AR is more similar to
                      the iodine analogue. With regard to the determination of
                      experimental logP values of radiohaloalkylated ligands, the
                      necessity of an improved procedure was revealed, as such
                      components may release halide, falsifying the experimental
                      results. Acknowledgements References [1] Holschbach M. H. et
                      al. (2002) J. Med. Chem., 45, 5150-5156. [2] Sihver W. et
                      al. (2003) Nucl. Med. Biol., 30, 661-668. [3] Breunig K. et
                      al. Radiochim. Acta (in press).},
      month         = {May},
      date          = {2015-05-26},
      organization  = {21st International Symposium on
                       Radiopharmaceutical Sciences, Columbia
                       (USA), 26 May 2015 - 31 May 2015},
      subtyp        = {Plenary/Keynote},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/825295},
}