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

Eur J Nucl Med Mol Imaging. 2003 Oct;30(10):1348-56. doi: 10.1007/s00259-003-1308-9. Epub 2003 Aug 21.


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 U343MGaCl2:1 (resistant to gefitinib). In both cell lines, the uptake of 211At-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 211At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with 211At-EGF alone. In A431 cells, 211At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. These results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours and decrease the effect of such therapy in gefitinib-sensitive tumours.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Astatine / therapeutic use*
  • Astrocytoma / drug therapy*
  • Astrocytoma / pathology
  • Astrocytoma / radiotherapy*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Combined Modality Therapy / methods
  • Epidermal Growth Factor / therapeutic use*
  • Gefitinib
  • Humans
  • Quinazolines / therapeutic use*
  • Radiopharmaceuticals / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents
  • Quinazolines
  • Radiopharmaceuticals
  • Epidermal Growth Factor
  • Gefitinib
  • Astatine