Assessment of epidermal growth factor receptor status in glioblastomas

Abstract

<em>Objective(s):</em> Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline ([¹²⁵I]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 [¹²⁵I] PYK in glioblastoma <em>in vitro</em> and <em>in vivo</em> to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment. <br/><em>Materials and Methods:</em> 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 [¹²⁵I]PYK were evaluated in cell lines <em>in vitro</em>. Tumor targeting of [¹²⁵I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT). <br/><em>R</em><em>esults:</em> High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [¹²⁵I] PYK in cell lines <em>in vitro</em> was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [¹²⁵I]PYK for xenografts showed no [¹²⁵I]PYK uptake. <br/><em>Conclusion:</em> The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [¹²⁵I]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.