% 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{Schneider:862365,
      author       = {Schneider, Daniela and Oskamp, Angela and Holschbach,
                      Marcus and Neumaier, Bernd and Bauer, Andreas and Bier,
                      Dirk},
      title        = {{R}elevance of {I}n {V}itro {M}etabolism {M}odels to {PET}
                      {R}adiotracer {D}evelopment: {P}rediction of {I}n {V}ivo
                      {C}learance in {R}ats from {M}icrosomal {S}tability {D}ata},
      journal      = {Pharmaceuticals},
      volume       = {12},
      number       = {2},
      issn         = {1424-8247},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {FZJ-2019-02699},
      pages        = {57},
      year         = {2019},
      abstract     = {The prediction of in vivo clearance from in vitro
                      metabolism models such as liver microsomes is an established
                      procedure in drug discovery. The potentials and limitations
                      of this approach have been extensively evaluated in the
                      pharmaceutical sector; however, this is not the case for the
                      field of positron emission tomography (PET) radiotracer
                      development. The application of PET radiotracers and
                      classical drugs differs greatly with regard to the amount of
                      substance administered. In typical PET imaging sessions,
                      subnanomolar quantities of the radiotracer are injected,
                      resulting in body concentrations that cannot be readily
                      simulated in analytical assays. This raises concerns
                      regarding the predictability of radiotracer clearance from
                      in vitro data. We assessed the accuracy of clearance
                      prediction for three prototypical PET radiotracers developed
                      for imaging the A1 adenosine receptor (A1AR). Using the
                      half-life (t1/2) approach and physiologically based scaling,
                      in vivo clearance in the rat model was predicted from
                      microsomal stability data. Actual clearance could be
                      accurately predicted with an average fold error (AFE) of
                      0.78 and a root mean square error (RMSE) of 1.6. The
                      observed slight underprediction (1.3-fold) is in accordance
                      with the prediction accuracy reported for classical drugs.
                      This result indicates that the prediction of radiotracer
                      clearance is possible despite concentration differences of
                      more than three orders of magnitude between in vitro and in
                      vivo conditions. Consequently, in vitro metabolism models
                      represent a valuable tool for PET radiotracer development.},
      cin          = {INM-2 / INM-5},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-2-20090406 / I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31013984},
      UT           = {WOS:000477028700012},
      doi          = {10.3390/ph12020057},
      url          = {https://juser.fz-juelich.de/record/862365},
}