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@ARTICLE{Schneider:868015,
      author       = {Schneider, Daniela and Oskamp, Angela and Holschbach,
                      Marcus and Neumaier, Bernd and Bier, Dirk and Bauer,
                      Andreas},
      title        = {{I}nfluence of binding affinity and blood plasma level on
                      cerebral pharmacokinetics and {PET} imaging characteristics
                      of two novel xanthine {PET} radioligands for the {A}1
                      adenosine receptor},
      journal      = {Nuclear medicine and biology},
      volume       = {82-83},
      issn         = {0969-8051},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {FZJ-2019-06608},
      pages        = {1 - 8},
      year         = {2020},
      abstract     = {The suitability of novel positron emission tomography (PET)
                      radioligands for quantitative in vivo imaging is affected by
                      various physicochemical and pharmacological parameters. In
                      this study, the combined effect of binding affinity,
                      lipophilicity, protein binding and blood plasma level on
                      cerebral pharmacokinetics and PET imaging characteristics of
                      three xanthine-derived A1 adenosine receptor (A1AR)
                      radioligands was investigated in rats.A comparative
                      evaluation of two novel cyclobutyl-substituted xanthine
                      derivatives,
                      8-cyclobutyl-3-(3-[18F]fluoropropyl)-1-propylxanthine
                      ([18F]CBX) and
                      3-(3-[18F]fluoropropyl)-8-(1-methylcyclobutyl)-1-propylxanthine
                      ([18F]MCBX), with the reference A1AR radioligand
                      8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine
                      ([18F]CPFPX) was conducted. This evaluation included in
                      vitro competition binding assays, in vitro autoradiography
                      and in vivo PET imaging. Differences in cerebral
                      pharmacokinetics and minimal scan duration required for
                      quantification of cerebral distribution volume (VT) were
                      assessed.Measured Ki values of non-labeled CBX, MCBX and
                      CPFPX were 10.0 ± 0.52 nM, 3.3 ± 0.30 nM and 1.4 ± 0.15
                      nM, respectively (n = 3–4). In vitro autoradiographic
                      binding patterns in rat brain were comparable between the
                      radioligands, as well as the fraction of non-specific
                      binding $(1.0–1.9\%).$ In vivo cerebral pharmacokinetics
                      of the novel cyclobutyl-substituted xanthines differed
                      considerably from that of [18F]CPFPX. Brain uptake and VT of
                      [18F]CBX were substantially lower despite the higher
                      concentration of radiotracer in plasma. [18F]MCBX showed
                      comparable uptake and VT, but faster cerebral kinetics than
                      [18F]CPFPX. However, the faster kinetics of [18F]MCBX did
                      not enable the quantification of cerebral VT in a shorter
                      scan time.The combined effect of individual physicochemical
                      and pharmacological properties of a radiotracer on its PET
                      imaging characteristics cannot be readily predicted. In vivo
                      performance of the xanthine A1AR radioligands was mainly
                      influenced by binding affinity; plasma concentrations and
                      cerebral kinetics were of secondary importance.},
      cin          = {INM-5 / INM-2},
      ddc          = {570},
      cid          = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31838339},
      UT           = {WOS:000528670200001},
      doi          = {10.1016/j.nucmedbio.2019.12.001},
      url          = {https://juser.fz-juelich.de/record/868015},
}