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Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with 211At-EGF
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Onko)
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2003 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, Vol. 30, no 10, 1348-56 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2003. Vol. 30, no 10, 1348-56 p.
Keyword [en]
Combined modality therapies, EGF, EGF receptor, 211At, Gefitinib
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-65769DOI: 10.1007/s00259-003-1308-9PubMedID: 12937952OAI: oai:DiVA.org:uu-65769DiVA: diva2:93680
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2015-03-24Bibliographically approved

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Orlova, AnnaTolmachev, Vladimir
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Department of Oncology, Radiology and Clinical Immunology
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