In vitro effects of free At-211, At-211-albumin and At-211-monoclonal antibody compared to external photon irradiation on two human cancer cell lines

Background The aim of this study was to perform various At-211 irradiations of importance for the evaluation of At-211-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation. Materi als and methods. All irradiations were performed on low-concentration singl e-cell suspensions. Growth assays wing 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of At-211. Results. A relative biological effect (R BE) of 12+/-2 (Colo-205) 211 and 5.3+/-0.7 (OVCAR-3) was found from At-211- albumin irradiations. There was a 174+/-28 times higher free At-211 concent ration in the cell fraction than in the surrounding medium. For At-211-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achiev ed, compared to the medium. Corrected for. the uptake an average of 31+/-2 ([At-211]- III astatine) ol 26+/-5 ([At-211]-MAb) decays per cell were requ ired for 37% survival of Colo-205 cells. An average of 19+/-3 decays ([At-2 11]-astatine) were required per; OVCAR-3 cell Conclusions. Cell uptake and binding of At-211 was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3+/-0.7 for OVCAR-3 and 12+/-2 for Colo-205 cells.