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

Åsa Liljegren Sundberg, Ylva Almqvist, Anna Orlova, Erik Blomquist, Holger J. Jensen, Lars Gedda, Vladimir Tolmachev, Jörgen Carlsson

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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 U343MGaC12:1 (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 211AtEGF 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.

Original languageEnglish
Pages (from-to)1348-1356
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume30
Issue number10
DOIs
Publication statusPublished - 1 Oct 2003
Externally publishedYes

Keywords

  • At
  • Combined modality therapies
  • EGF
  • EGF receptor
  • Gefitinib

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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