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 language | English |
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Pages (from-to) | 1348-1356 |
Number of pages | 9 |
Journal | European Journal of Nuclear Medicine and Molecular Imaging |
Volume | 30 |
Issue number | 10 |
DOIs | |
Publication status | Published - 1 Oct 2003 |
Externally published | Yes |
Keywords
- At
- Combined modality therapies
- EGF
- EGF receptor
- Gefitinib
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging