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 alpha-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) 211At-TP-3 of different specific activities, (b) 211At-labeled bovine serum albumin (BSA), (c) free 211At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, 211At-BSA or free 211At. The D0's were lower for free 211At than for 211At-BSA. The survival curves for 211At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to 211At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to 211At-TP-3 treatment was the antigen expression. Cell inactivation after 211At-TP-3 treatment increased substantially with increasing specific activity of the 211At-TP-3. At high specific activities, the cytotoxic effect of 211At-TP-3 was significantly higher than that of 211At-BSA. In conclusion, 211At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma.
Larsen
R H
RH
Department of Chemistry, University of Oslo, Norway.
Bruland
O S
OS
Hoff
P
P
Alstad
J
J
Lindmo
T
T
Rofstad
E K
EK
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001246:Astatine / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000532:radiotherapy*; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D012516:Osteosarcoma / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D012710:Serum Albumin, Bovine / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014965:X-Rays
D000911:Antibodies, Monoclonal; D012710:Serum Albumin, Bovine; D001246:Astatine