Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

Introduction: The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either Bi-213 or At-211, both alpha-emitters, in an ovarian cancer model. Methods: One hundred female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected intraperitoneally with similar to 2.7 MBq of Bi-213-MX35 (n=20) or similar to 0.44 MBq of At-211-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of Bi-213-MX35 (n=20) or At-211-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected Bi-213-MX35 and At-211-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16). Results: The animals injected with Bi-213-MX35 or At-211-MX35 2 weeks after cell inoculation had tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated reference group had a TFF of 0.20. The groups treated with Bi-213-MX35 or At-211-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of Bi-213-MX35 and At-211-MX35 were very similar to each other and displayed no alarming activity levels in the investigated organs. Conclusions: Micrometastatic growth of an ovarian cancer cell line was reduced in nude mice after treatment with Bi-213-MX35or. At-211-MX35. Treatment with At-211-MX35 provided a non-significantly better result for the chosen activity levels. The radiolabeled MX35 did not accumulate to a high extent in the investigated organs. No considerable signs of toxicity were observed. (C) 2012 Elsevier Inc. All rights reserved.