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Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity

By D. B. Axworthy, J. M. Reno, M. D. Hylarides, R. W. Mallett, L. J. Theodore, L. M. Gustavson, F.-M. Su, L. J. Hobson, P. L. Beaumier and A. R. Fritzberg

Abstract

A covalent conjugate (NR-LU-10/SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10/SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of 90Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600–800 μCi of 90Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm3) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2000
OAI identifier: oai:pubmedcentral.nih.gov:26516
Provided by: PubMed Central
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