Bismuth-213 radioimmunotherapy with C595 anti–MUC1 monoclonal antibody in an ovarian cancer ascites model

Abstract

Purpose: Control of ovarian cancer (OC) ascites remains a major objective in post-surgical treatment. The aim of this study was to investigate the effect of targeted alpha therapy (TAT) for the control of ascites in an OC ascites mouse model; the biodistribution of 213Bi-C595 and its long term toxicity. Methods: The expression of tumor-associated antigen mucin-1 (MUC-1) in OVCAR3 ascites cells in mice and OC cancer tissues in patients was detected by indirect immmunostaining. The monoclonal antibody (MAb) C595 was labeled with 213Bi using the chelator cDTPA to form the alpha-immunoconjugate (AIC). Mice were injected with different concentrations of AIC by i.p administration. Changes in tumor progression were assessed by measurement of the circumference of the abdomen. Results: MUC-1 is strongly expressed in 73% of OC tissues. At 9 days post-cell inoculation in mice, a single injection of 355 MBq/kg of 213Bi-C595 can prolong survival by 25 days. A high tumor: blood ratio (5.8) was found in biodistribution study. The maximum tolerance dose (MTD) was more than 1180 MBq/kg up to 21 weeks. Conclusions: C595 is a specific targeting vector for ovarian cancer cells, which show a high percentage of expression of MUC1. 213Bi-C595 can effectively target and kill ovarian cancer cells in vitro and in vivo. 213Bi-C595 is the recommended alpha conjugate for a Phase I clinical trial for ovarian cancer.