Radioimmunotherapy of experimental ovarian cancer with Astatine-211. An in vivo model for consolidation treatment in women

Abstract

About 850 new cases of ovarian cancer are diagnosed in Sweden every year. In 75 % of the patients the tumour has spread outside the ovaries. The standard treatment is surgery followed by six courses of combination chemotherapy. In spite of a very high frequency of clinical complete responses the 5-year survival is not satisfactory. Thus there is a great need for consolidating therapy.Radioimmunotherapy (RIT), i.e. treatment with specific monoclonal antibodies (MAb) labelled with radionuclides has been tried for various tumours experimentally and clinically. In most studies b-emitters have been used but for micrometastases an a-emitter with a very short tissue range may be better.The purpose of this study was to examine the in vitro effect of the a-emitter Astatine-211 (211At) and to investigate the therapeutic efficacy of regional administration of the specific antibody MOv18 labelled with 211At to nude mice with intraperitoneal growth of human ovarian cancer. Methods. For the in vitro studies the two human cancer cell lines NIH:OVCAR-3 and Colo-205 were used. Cell suspensions were treated with free 211At, 211At-albumin, 211At-Mab or with photon irradiation. The human ovarian cancer cell line NIH:OVCAR-3 was used for the in vivo studies. Two weeks after the inoculation of cells, when the tumour still was microscopic, 211At-MOv18 was injected intraperitoneally. The therapeutic effect was evaluated six weeks later except in the long-term studyResults. In vitro the uptake of free 211At on both cell lines was unexpectedly high. A low number (19-31) of 211At decays on the cell surface was needed for 37% cell survival for both cell types.In the short term in vivo studies 18 of 20 mice were tumour-free when 211At-MOv18 was injected i.p. In the long-term study the survival was significantly better for treated than for untreated mice. Thirty-three per cent of the animals were tumour-free at the end of the study.Conclusion. Intraperitoneal radioimmunotherapy with an 211At-labelled specific antibody is an effective treatment of human ovarian cancer growing in nude mice. Hopefully, this treatment will be of value as consolidating treatment in women with minimal residual disease after surgery and chemotherapy