Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian cancer model.
Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with 90Y-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 90Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between 90Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera.
Kairemo
K
K
Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
Ljunggren
K
K
Strand
S E
SE
Hiltunen
J
J
Penttilä
P
P
Nikula
T
T
Laine
A
A
Wahlström
T
T
D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D016019:Survival Analysis; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; D005337:Fibrin