Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity
DB Axworthy, JM Reno, MD Hylarides… - Proceedings of the …, 2000 - National Acad Sciences
DB Axworthy, JM Reno, MD Hylarides, RW Mallett, LJ Theodore, LM Gustavson, FM Su…
Proceedings of the National Academy of Sciences, 2000•National Acad SciencesA 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 …
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 …
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.
National Acad Sciences