Assessment of Epidermal Growth Factor Receptor Status in Glioblastomas.

OBJECTIVES: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.CONCLUSION: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.