Open AccessCure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity
Author(s) -
Donald B. Axworthy,
John M. Reno,
Mark D. Hylarides,
Robert Mallett,
Louis Theodore,
L. M. Gustavson,
Shuangshuang Fu,
Lori J. Hobson,
Paul L. Beaumier,
Alan R. Fritzberg
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.4.1802
Subject(s) - conjugate , radioimmunotherapy , toxicity , biotinylation , chemistry , biotin , streptavidin , cancer research , medicine , pharmacology , microbiology and biotechnology , antibody , monoclonal antibody , immunology , biology , biochemistry , mathematical analysis , mathematics
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 of90 Y-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 of90 Y-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.