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

Journal article
Authors Anna Gustafsson
Tom Bäck
Jörgen Elgqvist
Lars Jacobsson
Ragnar Hultborn
Per Albertsson
Alfred Morgenstern
Frank Bruchertseifer
Holger Jensen
Sture Lindegren
Published in Nuclear medicine and biology
Volume 39
Issue 1
Pages 15–22
ISSN 1872-9614
Publication year 2012
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Oncology
Pages 15–22
Language en
Links dx.doi.org/10.1016/j.nucmedbio.2011...
Subject categories Cancer and Oncology, Radiological research

Abstract

INTRODUCTION: The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, 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 (213)Bi-MX35 (n=20) or ∼0.44 MBq of (211)At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of (213)Bi-MX35 (n=20) or (211)At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected (213)Bi-MX35 and (211)At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16). RESULTS: The animals injected with (213)Bi-MX35 or (211)At-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 (213)Bi-MX35 or (211)At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of (213)Bi-MX35 and (211)At-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 (213)Bi-MX35or (211)At-MX35. Treatment with (211)At-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.

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