Simonson R B, Ultee M E, Hauler J A, Alvarez V L
CYTOGEN Corporation, Princeton, New Jersey 08540.
Cancer Res. 1990 Feb 1;50(3 Suppl):985s-988s.
212Bi is a radioisotope that emits highly cytotoxic alpha-particles. alpha-particles have a high linear energy transfer over a short path length. These properties and the 1-h half-life make this isotope suitable for radioimmunotherapy of peritoneal tumors. Therefore, we wanted to test whether monoclonal antibodies labeled with 212Bi would be effective in treating such tumors. We conjugated the antibody B72.3, which is reactive with many human adenocarcinomas, to the chelator linker glycyltyrosyl-lysyl-N-epsilon-diethylenetriaminepentaacetic acid, by reductive amination to the carbohydrate residues of the antibody (J. Rodwell, et al. Proc. Natl. Acad. Sci. USA, 83: 2632-2636, 1986). Athymic nude mice were injected i.p. with LS174T cells, a human colon cancer cell line. Seven to 13 days later the mice were treated with the 212Bi-labeled antibody. We treated the mice using single doses of 180-450 microCi or multiple doses of 80-180 microCi on consecutive days. Dissections were performed 9-16 days after the end of treatment. Both the single and multiple doses resulted in a decrease in tumor burden when compared to tumor from mice receiving unlabeled antibody. Mice in the optimum group showed tumor reductions of greater than 90%. Treatment with a 212Bi-labeled irrelevant antibody was significantly less effective than that with labeled B72.3 antibody. Survival studies showed that mice receiving the labeled antibody had a prolonged survival when compared to control mice.
212Bi是一种发射具有高度细胞毒性的α粒子的放射性同位素。α粒子在短路径长度上具有高传能线密度。这些特性以及1小时的半衰期使得这种同位素适用于腹膜肿瘤的放射免疫治疗。因此，我们想测试用212Bi标记的单克隆抗体治疗此类肿瘤是否有效。我们通过还原胺化作用将与多种人类腺癌反应的抗体B72.3与螯合剂连接体甘氨酰酪氨酰赖氨酰-N-ε-二亚乙基三胺五乙酸结合到抗体的碳水化合物残基上（J.罗德韦尔等人，《美国国家科学院院刊》，83: 2632 - 2636, 1986）。给无胸腺裸鼠腹腔注射人结肠癌细胞系LS174T细胞。7至13天后，用212Bi标记的抗体治疗小鼠。我们对小鼠使用180 - 450微居里的单剂量或连续几天使用80 - 180微居里的多剂量进行治疗。在治疗结束后9至16天进行解剖。与接受未标记抗体的小鼠的肿瘤相比，单剂量和多剂量治疗均导致肿瘤负荷降低。最佳组的小鼠肿瘤缩小超过90%。用212Bi标记的无关抗体治疗的效果明显低于用标记的B72.3抗体治疗的效果。生存研究表明，与对照小鼠相比，接受标记抗体治疗的小鼠生存期延长。
