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

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.

• Authors: D B Axworthy, J M Reno, M D Hylarides, R W Mallett, L J Theodore, L M Gustavson, F Su, L J Hobson, P L Beaumier, A R Fritzberg
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 4 Pg. 1802-7 (Feb 15 2000) ISSN: 0027-8424 [Print] United States
• PMID: 10677537 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Antineoplastic Agents
• Cell Adhesion Molecules
• Chelating Agents
• Epithelial Cell Adhesion Molecule
• Heterocyclic Compounds, 1-Ring
• Radiopharmaceuticals
• Yttrium Radioisotopes
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Topics

• Animals
• Antibodies, Monoclonal
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents (blood, pharmacology)
• Carcinoma (metabolism)
• Cell Adhesion Molecules (immunology)
• Chelating Agents (chemistry)
• Colonic Neoplasms (drug therapy, immunology)
• Epithelial Cell Adhesion Molecule
• Heterocyclic Compounds, 1-Ring (chemistry)
• Humans
• Mice
• Mice, Nude
• Molecular Structure
• Neoplasm Transplantation
• Radioimmunotherapy (methods)
• Radiopharmaceuticals (therapeutic use, toxicity)
• Transplantation, Heterologous
• Yttrium Radioisotopes (therapeutic use, toxicity)