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

Purpose: This study was designed to compare the cytotoxic effects of an alp ha-emitting radioimmunoconjugate, which hinds to osteosarcoma but not to bo ne marrow cells, with those of external gamma-irradiation. Materials and methods: The human osteosarcoma cell line, OHS-sl, and mononu clear cells from bone marrow (BM) harvested from healthy donors, were used for these experiments. Cells in suspension were added to various activity c oncentrations of the and-osteosarcoma monoclonal antibody TP-3 radiolabelle d with At-211. Following incubation for 1h, unbound radioactivity was washe d off and cell survival was determined from clonogenic assays. Microdosimet ry was calculated based on binding and retention kinetics of At-211 to the cells, as well as cellular and nuclear diameters. For comparison, cell susp ensions were irradiated with a single dose of Co-60 gamma-rays. Results: At-211-labelled TP-3 showed heterogeneous binding to OHS-sl cells, with a considerable variation among experiments. About 78% of the initiall y bound At-211 decayed while associated with the OHS-sl cells. D-0 values e stimated by microdosimetry were 0.33 (0.22-0.48, range) Gy and 1.18 (0.89-1 .89) Gy for OHS-sl and BM cells, respectively, whereas D-0 values after ext ernal beam irradiation were 0.86+/-0.07 Gy and 1.71+/-0.22 Gy. The relative biological effectiveness (RBE) of At-211-labelled TP-3 at 37% survival was 3.43 for OHS-sl and 1.55 for BM. Conclusions: High-LET targeted alpha-particle exposure killed osteosarcoma cells more effectively than bone marrow cells, although heterogeneous antig en expression among these tumour cells limited the magnitude of this effect .