title: Assessment of epidermal growth factor receptor status in glioblastomas.
abstract: OBJECTIVE
  Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline ([(125)I]PYK) is promising for the evaluation of the epidermal growth factor receptor (EGFR) status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the expressions and mutation of EGFR were tested with [(125)I] PYK in glioblastoma in vitro and in vivo to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment.
  
  
  METHODS
  Glioblastoma cell lines with different expression of EGFR were tested. Growth inhibition of cell lines by gefitinib was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Uptake levels of [(125)I]PYK were evaluated in cell lines in vitro. Tumor targeting of [(125)I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT).
  
  
  RESULTS
  High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [(125)I] PYK in cell lines in vitro was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [(125)I]PYK for xenografts showed no [(125)I]PYK uptake.
  
  
  CONCLUSIONS
  The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [(125)I]PYK, which might be due to the complicated expression of EGFR status in glioblastoma. Thus, new tracers for sites downstream of the mutant EGFR should be investigated in further studies.
authors.affiliation: Department of Radiology, Hamamatsu University School of Medicine, Japan.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhu
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
authors.affiliation: Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ohmomo
authors.affiliation: Department of Neurosurgery, Hamamatsu University School of Medicine, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
authors.affiliation: Department of Radiology, Hamamatsu University School of Medicine, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Sakahara
keywords: EGFR; Gefitinib; Glioblastoma; [125I]PYK