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Journal of Oncology
Volume 2010 (2010), Article ID 394913, 5 pages
http://dx.doi.org/10.1155/2010/394913
Research Article

Repeated Intraperitoneal 𝛼 -Radioimmunotherapy of Ovarian Cancer in Mice

1Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
2PET and Cyclotron Unit, Rigshospitalet, Copenhagen, Denmark

Received 15 April 2009; Accepted 1 September 2009

Academic Editor: Maurie M. Markman

Copyright © 2010 Jörgen Elgqvist et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aim of this study was to investigate the therapeutic efficacy of 𝛼 -radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F ( a b  ) 2 labeled with the 𝛼 -particle emitter 2 1 1 A t . Methods. Nude mice were intraperitoneally inoculated with ~ 1 × 1 0 7 cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given 4 0 0 k B q 2 1 1 A t - M X 3 5 F ( a b  ) 2 as a single or as a repeated treatment of up to 6 times ( 𝑛 = 1 8 in each group). The fractionated treatments were given every seventh day. Control animals were treated with unlabeled M X 3 5 F ( a b  ) 2 ( 𝑛 = 1 2 ). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals with no macro- and microtumors and no ascites, were 0.17, 0.11, 0.39, 0.44, 0.44, and 0.67 when treated with 4 0 0 k B q 2 1 1 A t - M X 3 5 F ( a b  ) 2 once or 2, 3, 4, 5, or 6 times, respectively. Repeated treatment 3 times or more resulted in a significantly higher ( 𝑃 < . 0 5 ) TFF than compared to treatment once or twice. The presence of ascites decreased from 15 out of 18 animals in the group given only one treatment to zero for the 2 groups given 5 or 6 fractions. Treatment with unlabeled M X 3 5 F ( a b  ) 2 resulted in a TFF of zero. Conclusion. Weekly repeated intraperitoneal injections of tolerable amounts of activity of 2 1 1 A t - M X 3 5 F ( a b  ) 2 of up to 6 times produced increased therapeutic efficacy without observed toxicity, indicating a potential increase of the therapeutic index.