K. Kairemo et al., RADIOIMMUNOTHERAPY WITH Y-90 LABELED MONOCLONAL-ANTIBODIES IN A NUDE-MOUSE OVARIAN-CANCER MODEL, Acta oncologica, 32(7-8), 1993, pp. 801-805
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.