α-Particle Radioimmunotherapy of Disseminated Peritoneal Disease Using a 212Pb-Labeled Radioimmunoconjugate Targeting HER2

These studies demonstrate the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using 212Pb-labeled Herceptin as an in vivo generator of 212Bi. In vitro studies compare the potential of the bismuth radioisotopes, 213Bi and 212Bi, to that of 212Pb. Overall, 212Pb results in a higher therapeutic index than either bismuth radioisotope, requiring lower radioactivity (µCi) for effective cytotoxic response. A pilot radioimmunotherapy (RIT) experiment treating mice bearing 5 d LS-174T intraperitoneally (i.p.) xenografts determined a maximum tolerated dose (MTD) of 20–40 µCi with i.p. administration. A specific dose response was observed and 10 µCi was selected as the effective operating dose for future experiments. Median survival of tumor-bearing mice receiving 10 µCi increased from 19 to 56 days (p = 0.008). The efficacy of 212Pb-Herceptin was also assessed in a human pancreatic carcinoma xenograft (Shaw; i.p.) animal model previously reported as unresponsive to 213Bi-Hercept...