RADIOIMMUNOTHERAPY WITH Y-90 LABELED MONOCLONAL-ANTIBODIES IN A NUDE-MOUSE OVARIAN-CANCER MODEL

Tumor stroma contains much fibrin, and so monoclonal antifibrin antibo dy can accumulate in tumors. We treated nude mice bearing human ovaria n carcinoma xenografts,vith Y-90-labeled monoclonal antifibrin antibod y Fab fragments administered intratumorally. The survival time vs. a c ontrol group was significantly prolonged and tumor growth rate was dec reased. Another group of animals was treated with Y-90-labeled OC 125- monoclonal antibody; these mice received the antibodies intratumorally , intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between Y-90-labeled OC 125 and antifibrin in the intratu morally treated animal groups. The tissue activity distribution studie s revealed that bone marrow is the critical organ. Intratumorally inje cted monoclonal Y-90-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenogra ft after one treatment, causing cell death. Beta-camera imaging and im munohistochemistry were performed for studies of the correlation betwe en Y-90 activity and fibrin distribution in tumor specimens. These res ults were in concordance. Tn conclusion, intratumoral administration s eems suitable for radioimmunotherapy, with an antibody that targets st romal structures. The accumulation can be successfully monitored by a beta-camera.