Repeated Intraperitoneal α-Radioimmunotherapy of Ovarian Cancer in Mice

Abstract EN

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(ab′)2 labeled with the α-particle emitter A211t.

Methods.

Nude mice were intraperitoneally inoculated with ~1×107 cells of the cell line NIH:OVCAR-3.

Four weeks later 6 groups of animals were given 400 kBq 211At-MX35 F(ab′)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 unlabeled MX35 F(ab′)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 with 400 kBq 211At-MX35 F(ab′)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 unlabeled MX35 F(ab′)2 resulted in a TFF of zero.

Conclusion.

Weekly repeated intraperitoneal injections of tolerable amounts of activity of A211t-MX35 F(ab′)2 of up to 6 times produced increased therapeutic efficacy without observed toxicity, indicating a potential increase of the therapeutic index.