% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Humpert:1025522,
      author       = {Humpert, Swen and Schneider, Daniela and Bier, Dirk and
                      Schulze, Annette and Neumaier, Felix and Neumaier, Bernd and
                      Holschbach, Marcus},
      title        = {8-{B}icycloalkyl-{CPFPX} derivatives as potent and
                      selective tools for in vivo imaging of the {A}1 adenosine
                      receptor},
      journal      = {European journal of medicinal chemistry},
      volume       = {271},
      issn         = {0009-4374},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {FZJ-2024-02916},
      pages        = {116380},
      year         = {2024},
      abstract     = {Imaging of the A1 adenosine receptor (A1R) by positron
                      emission tomography (PET) with
                      8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propyl-xanthine
                      ([18F]CPFPX) has been widely used in preclinical and
                      clinical studies.However, this radioligand suffers from
                      rapid peripheral metabolism and subsequent accumulation of
                      radiometabolites in the vascular compartment. In the present
                      work, we prepared four derivatives of CPFPX byreplacement of
                      the cyclopentyl group with norbornane moieties. These
                      derivatives were evaluated by competition binding studies,
                      microsomal stability assays and LC-MS analysis of microsomal
                      metabolites. In addition, the18F-labeled isotopologue of
                      8-(1-norbornyl)-3-(3-fluoropropyl)-1-propylxanthine (1-NBX)
                      as the most promising candidate was prepared by
                      radiofluorination of the corresponding tosylate precursor
                      and the resulting radioligand([18F]1-NBX) was evaluated by
                      permeability assays with Caco-2 cells and in vitro
                      autoradiography in rat brain slices. Our results demonstrate
                      that 1-NBX exhibits significantly improved A1R affinity and
                      selectivity whencompared to CPFPX and that it does not give
                      rise to lipophilic metabolites expected to cross the
                      blood-brain-barrier in microsomal assays. Furthermore,
                      [18F]1-NBX showed a high passive permeability (Pc = 6.9 ±
                      2.9 × 10􀀀 5 cm/s) and in vitro autoradiography with this
                      radioligand resulted in a distribution pattern matching A1R
                      expression in the brain. Moreover, a low degree of
                      non-specific binding $(5\%)$ was observed. Taken together,
                      these findings identify [18F]1-NBX as a promising candidate
                      for further preclinicalevaluation as potential PET tracer
                      for A1R imaging.},
      cin          = {INM-5},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38615410},
      UT           = {WOS:001229721600001},
      doi          = {10.1016/j.ejmech.2024.116380},
      url          = {https://juser.fz-juelich.de/record/1025522},
}