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 (90)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 microCi of (90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm(3)) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity.
MeSH terms
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Animals
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Antibodies, Monoclonal
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Antigens, Neoplasm / immunology
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Antineoplastic Agents / blood
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Antineoplastic Agents / pharmacology
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Carcinoma / metabolism*
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Cell Adhesion Molecules / immunology
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Chelating Agents / chemistry
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / immunology
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Epithelial Cell Adhesion Molecule
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Heterocyclic Compounds, 1-Ring / chemistry
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Humans
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Mice
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Mice, Nude
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Molecular Structure
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Neoplasm Transplantation*
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Radioimmunotherapy / methods
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Radiopharmaceuticals / therapeutic use
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Radiopharmaceuticals / toxicity
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Transplantation, Heterologous*
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Yttrium Radioisotopes* / therapeutic use*
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Yttrium Radioisotopes* / toxicity
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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Antineoplastic Agents
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Cell Adhesion Molecules
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Chelating Agents
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Epithelial Cell Adhesion Molecule
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Heterocyclic Compounds, 1-Ring
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Radiopharmaceuticals
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Yttrium Radioisotopes
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1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid