RADIOIMMUNOTHERAPY OF NEOPLASTIC MENINGITIS IN RATS USING AN ALPHA-PARTICLE-EMITTING IMMUNOCONJUGATE

Because of their short range and high linear energy transfer, alpha-pa rticles may be particularly effective in the treatment of neoplastic m eningitis. Monoclonal antibody 81C6 was labeled with alpha-particle-em itting At-211 using N-succinimidyl3-[At-211]astatobenzoate, and the ef ficacy and toxicity of this immunoconjugate were evaluated in an athym ic rat model. Animals were given injections via a chronic indwelling c atheter with 5 x 10(5) TE-671 human rhabdomyosarcoma cells and treated 8 days later with single intrathecal doses of either saline or 4-18 m u Ci of At-211-labeled specific 81C6 antibody or isotype matched contr ol At-211-labeled 45.6 antibody. In the first experiment, 4, 7, and 13 mu Ci At-211-labeled 81C6 produced statistically significant (P = 0.0 04-0.02) increases in median survival of 33, 29, and 51%, respectively , as compared with saline. Two of 10 animals receiving the 13-mu Ci do se lived for 6 months before being killed for histological analysis. I n the second experiment, 12 mu Ci of At-211-labeled 45.6 did not incre ase median survival significantly relative to saline control, while 12 mu Ci of At-211-labeled 81C6 increased median survival by 113% (P < 0 .005) and resulted in 33% apparent cures. Five of 10 animals receiving 18 mu Ci of At-211-labeled 81C6 survived until they were killed at 29 5 days. An additional study was performed in animals given intrathecal injections of 5 x 10(6) TE-671 cells and given a single dose of 18 mu Ci of At-211-labeled 81C6 or At-211-labeled 45.6. At this higher cell number, significantly prolonged survival was still seen for specific antibody as compared with saline (P < 0.001) and control antibody (P < 0.05). These results suggest that treatment with At-211-labeled monoc lonal antibodies may be a valuable approach for neoplastic meningitis.