Exposure of human osteosarcoma and bone marrow cells to tumour-targeted α-particles and γ-irradiation: analysis of cell survival and microdosimetry

Purpose : This study was designed to compare the cytotoxic effects of an α -emitting radioimmunoconjugate, which binds to osteosarcoma but not to bone marrow cells, with those of external γ-irradiation. Materials and methods : The human osteosarcoma cell line, OHSs1, and mononuclear cells from bone marrow (BM) harvested from healthy donors, were used for these experiments. Cells in suspension were added to various activity concentrations of the anti-osteosarcoma monoclonal antibody TP-3 radiolabelled with 211 At. Following incubation for 1 h, unbound radioactivity was washed off and cell survival was determined from clonogenic assays. Microdosimetry was calculated based on binding and retention kinetics of 211 At to the cells, as well as cellular and nuclear diameters. For comparison, cell suspensions were irradiated with a single dose of 60 Co γ-rays. Results : 211 At-labelled TP-3 showed heterogeneous binding to OHS-s1 cells, with a considerable variation among experiments. About 78% of the initially bo...