Radioimmunotherapy with Alpha-Particle-Emitting Immunoconjugates

TLDR

Alpha particles are energetic short‑range ions whose high linear energy transfer causes extreme cytotoxicity. The authors prepared a bismuth‑212‑labeled IgM radioimmunoconjugate that targets the Thy 1.2 antigen on murine T cells. The conjugate selectively killed Thy 1.2‑positive EL‑4 tumor cells in vitro, with ~3 molecules per cell eliminating DNA synthesis, and cured ascites in mice after 150 µCi intraperitoneal injection, suggesting therapeutic promise.

Abstract

Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An α-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2 + EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [ 3 H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.