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@ARTICLE{Stegmayr:827963,
      author       = {Stegmayr, Carina and Oliveira, Dennis and Niemietz, Nicole
                      and Willuweit, Antje and Lohmann, Philipp and Galldiks,
                      Norbert and Shah, N. J. and Ermert, Johannes and Langen,
                      Karl-Josef},
      title        = {{I}nfluence of bevacizumab on blood-brain barrier
                      permeability and {O}-(2- 18 {F}-fluoroethyl)-{L}-tyrosine
                      uptake in rat gliomas},
      journal      = {Journal of nuclear medicine},
      volume       = {58},
      number       = {5},
      issn         = {2159-662X},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {FZJ-2017-01991},
      pages        = {700-705},
      year         = {2017},
      abstract     = {Restoration of the blood–brain barrier (BBB) after
                      antiangiogenic therapy of gliomas with bevacizumab may
                      result in a decrease in contrast enhancement on MRI despite
                      tumor progression. This so-called pseudoresponse is
                      difficult to differentiate from a true tumor response with
                      conventional MRI. Initial patient studies have indicated
                      that PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET)
                      may be helpful for solving this diagnostic problem. This
                      study was performed to investigate the effects of
                      bevacizumab on BBB permeability and 18F-FET uptake in a
                      human xenograft model. Methods: Human U87 glioblastoma cells
                      were implanted into the striatum of immunodeficient RNU
                      rats. 18F-FET PET scans and ex vivo autoradiography were
                      performed in animals receiving a single high dose of
                      bevacizumab (45 mg/kg 2 d before PET; n = 9) or in animals
                      receiving 2 lower doses (10 mg/kg 9 and 2 d before PET; n =
                      10) to evaluate short-term and long-term effects on the BBB,
                      respectively, and in control animals without bevacizumab
                      treatment (n = 8). Time–activity curves, slope, and
                      tumor-to-brain ratios of 18F-FET uptake (18–61 min after
                      injection) were evaluated using a volume-of-interest
                      analysis. After PET scanning, Evans blue dye (EBD) was
                      injected into animals, and cryosections of the brains were
                      evaluated by autoradiography, by histology, and for EBD
                      fluorescence to assess BBB permeability. Results: Compared
                      with the control, short-term bevacizumab therapy resulted in
                      a trend toward BBB restoration (P = 0.055) and long-term
                      therapy resulted in a significant decrease (P = 0.004) in
                      BBB permeability, as assessed by EBD fluorescence. In
                      contrast, no significant differences in tumor-to-brain
                      ratios or slope of 18F-FET uptake were observed in PET and
                      autoradiography (P > 0.05). Conclusion: 8F-FET uptake in
                      glioblastomas seems to be largely independent of BBB
                      permeability and reflects the viability of tumor tissue
                      during antiangiogenic therapy more reliably than
                      contrast-enhanced MRI},
      cin          = {INM-3 / INM-4 / INM-5},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)INM-4-20090406 /
                      I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000400633500008},
      doi          = {10.2967/jnumed.116.187047},
      url          = {https://juser.fz-juelich.de/record/827963},
}