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

Abstract 

Introduction

The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either ²¹³Bi or ²¹¹At, both α-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 ∼2.7 MBq of ²¹³Bi-MX35 (n=20) or ∼0.44 MBq of ²¹¹At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of ²¹³Bi-MX35 (n=20) or ²¹¹At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected ²¹³Bi-MX35 and ²¹¹At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16).

Results

The animals injected with ²¹³Bi-MX35 or ²¹¹At-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 ²¹³Bi-MX35 or ²¹¹At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of ²¹³Bi-MX35 and ²¹¹At-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 ²¹³Bi-MX35or ²¹¹At-MX35. Treatment with ²¹¹At-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.

Keywords: Radioimmunotherapy, Bismuth, Astatine, MX35, α-Particle