Inactivation of Human Osteosarcoma Cells In Vitro by ²¹¹At-TP-3 Monoclonal Antibody: Comparison with Astatine-211-Labeled Bovine Serum Albumin, Free Astatine-211 and External-Beam X Rays

The potential usefulness of α-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a)${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ of different specific activities, (b)${}^{211}{\rm At}\text{-labeled}$ bovine serum albumin (BSA), (c) free${}^{211}{\rm At}$ and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays,${}^{211}{\rm At}\text{-}{\rm BSA}$ or free${}^{211}{\rm At}$. The$D_{0}\text{'}{\rm s}$ were lower for free${}^{211}{\rm At}$ than for${}^{211}{\rm At}\text{-}{\rm BSA}$. The survival curves for${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ treatment was the antigen expression. Cell inactivation after${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ treatment increased substantially with increasing specific activity of the${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$. At high specific activities, the cytotoxic effect of${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ was significantly higher than that of${}^{211}{\rm At}\text{-}{\rm BSA}$. In conclusion,${}^{211}{\rm At}\text{-}{\rm TP}\text{-}3$ has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma.