Repeated Intraperitoneal α-Radioimmunotherapy of Ovarian Cancer in Mice. (25th October 2009)

• Record Type: Journal Article
• Authors: Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger; Kahu, Helena; Lindegren, Sture; Warnhammar, Elisabet; Hultborn, Ragnar
• Other Names: Markman Maurie M. Academic Editor.
• Is Part Of: Journal of oncology. Volume 2010(2010)
• Publication Date: 2009-10-25
• Subjects: Oncology -- Research -- Periodicals; Tumors -- Periodicals; Neoplasms; Oncology -- Research; Tumors; Periodicals; Periodicals; 616.994
• DOI: 10.1155/2010/394913
• Languages: English
• ISSNs: 1687-8450

Abstract

Abstract : The aim of this study was to investigate the therapeutic efficacy ofα -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 theα -particle emitterA 211 t . Methods . Nude mice were intraperitoneally inoculated with ~1 × 10 7 cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given400 kBq 211 At-MX35 F( a b ′ ) 2 as a single or as a repeated treatment of up to 6 times (n = 18 in each group). The fractionated treatments were given every seventh day. Control animals were treated with unlabeledMX35 F( a b ′ ) 2 (n = 12 ). 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 with400 kBq 211 At-MX35 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 < .05 ) 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 unlabeledMX35 F( a b ′ ) 2 resulted in a TFF of zero. Conclusion . Weekly repeated intraperitoneal injections of tolerable amounts of activity ofA 211 t-MX35 F( a b ′ ) 2 of up to 6 times produced increased therapeutic efficacy without observed toxicity, indicating a potential increase of the therapeutic index.