Combined effect of gefitinib flressa', ZD1839) and targeted radiotherapy with ~(211)At-EGF

摘要

Abstract. The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ['Iressa' (trademark of the AstraZeneca group of companies), ZD1839] increases the cellular uptake of radiolabelled epidermal growth factor (EGF). We investigated gefitinib treatment combined with astatine-211 EGF targeting in vitro using two cell lines expressing high levels of EGFR: A431 (sensitive to gefitinib) and U343MOaC12:1 (resistant to gefitinib). In both cell lines, the uptake of ~(211)At-EGF was markedly increased by concomitant treatment with gefitinib. Survival was investigated using both a clonogenic survival assay and a cell growth assay. Combined gefitinib and ~(211)At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with~(211)At-EGF alone. In A431 cells, ~(211)At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. The|e results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours land decrease the effect of such therapy in gefitinib-sensitive tumours.