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@ARTICLE{Mauler:878189,
      author       = {Mauler, Jörg and Heinzel, Alexander and Matusch, Andreas
                      and Herzog, Hans and Neuner, Irene and Scheins, Jürgen and
                      Wyss, Christine and Dammers, Jürgen and Lang, Markus and
                      Ermert, Johannes and Neumaier, Bernd and Langen, Karl-Josef
                      and Shah, N. Jon},
      title        = {{B}olus infusion scheme for the adjustment of steady state
                      [11{C}]{F}lumazenil levels in the grey matter and in the
                      blood plasma for neuroreceptor imaging},
      journal      = {NeuroImage},
      volume       = {221},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2020-02677},
      pages        = {117160 -},
      year         = {2020},
      abstract     = {The use of hybrid PET/MR imaging facilitates the
                      simultaneous investigation of challenge-related changes in
                      ligand binding to neuroreceptors using PET, while
                      concurrently measuring neuroactivation or blood flow with
                      MRI. Having attained a steady state of the PET radiotracer
                      using a bolus-infusion protocol, it is possible to observe
                      alterations in ligand neuroreceptor binding through changes
                      in distribution volumes. Here, we present an iterative
                      procedure for establishing an administration scheme to
                      obtain steady state [11C]flumazenil concentrations in grey
                      matter in the human brain. In order to achieve a steady
                      state in the shortest possible time, the bolus infusion
                      ratio from a previous examination was adapted to fit the
                      subsequent examination. 17 male volunteers were included in
                      the study. Boli and infusions with different weightings were
                      given to the subjects and were characterised by values from
                      74 ​min down to 42 ​min. Metabolite analysis was used to
                      ascertain the value of unmetabolised flumazenil in the
                      plasma, and PET imaging was used to assess its binding in
                      the grey matter. The flumazenil time-activity curves (TACs)
                      in the brain were decomposed into activity contributions
                      from pure grey and white matter and analysed for 12 ​vol
                      of interest (VOIs). The curves highlighted a large
                      variability in metabolic rates between the subjects, with
                      ​= ​54.3 ​min being a reliable value to provide
                      flumazenil equilibrium conditions in the majority of the
                      VOIs and cases. The distribution volume of flumazenil in all
                      12 VOIs was determined.},
      cin          = {INM-4 / INM-11 / JARA-BRAIN / INM-5 / INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-11-20170113 /
                      I:(DE-Juel1)VDB1046 / 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:32679251},
      UT           = {WOS:000600795000025},
      doi          = {10.1016/j.neuroimage.2020.117160},
      url          = {https://juser.fz-juelich.de/record/878189},
}