title: External beam radiation enhances antibody mediated radiocytotoxicity in human glioma cells in vitro.
abstract: Enhanced accumulation of monoclonal antibodies in tumor tissue has been observed as a result of external beam irradiation (EBR). This effect was mainly attributed to increased vascular leakage due to unspecific radiation damage of vascular endothelial cells. The aim of this study was to investigate the effects of EBR on expression and antibody-binding of epidermal growth-factor receptor (EGF-R) in human glioma cells in-vitro. High-grade glioma cells were irradiated with conventional x-rays (0-3600 Rad) and surface binding, internalization and radiocytotoxicity of 125I-labeled monoclonal antibody (MAb) 425, specific for human EGF-R, was tested. EBR showed a short-term dose and time dependent increase of specific MAb 425 binding and internalization in receptor positive cell lines U87-MG and A1207. This effect was probably due to a mitotic block and an increase in cellular volume. Combination of EBR and 125I-425 showed additive effects on cell vitality/survival and was more pronounced in contact inhibited cells as compared to cells growing in a log-phase. We assume that cells exposed to 125I-labeled MAb 425 are only able to accumulate a critical number of DNA double-strand breaks when the doubling-time is prolonged e.g. under contact-inhibition or radiation induced mitotic blockade. We conclude that EBR has no negative effects on EGF-R expression, MAb-binding and internalization. The combination of EBR and 125I-MAb 425 enhances cytotoxic efficacy and thus supports adjuvant use in the clinical management of high-grade glioma.
authors.affiliation: Department of Nuclear Medicine, University of Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bender
authors.forename: J G
authors.initials: JG
authors.lastname: Emrich
authors.forename: J
authors.initials: J
authors.lastname: Eshelman
authors.forename: M A
authors.initials: MA
authors.lastname: Chu
authors.forename: Z
authors.initials: Z
authors.lastname: Steplewski
authors.forename: H J
authors.initials: HJ
authors.lastname: Biersack
authors.forename: L W
authors.initials: LW
authors.lastname: Brady
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007700:Kinetics; D051379:Mice; D016499:Radioimmunotherapy / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D066246:ErbB Receptors