Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity.
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.
Axworthy
D B
DB
NeoRx Corporation, Seattle, WA 98119, USA. daxworthy@neorx.com
Reno
J M
JM
Hylarides
M D
MD
Mallett
R W
RW
Theodore
L J
LJ
Gustavson
L M
LM
Su
F
F
Hobson
L J
LJ
Beaumier
P L
PL
Fritzberg
A R
AR
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002614:Chelating Agents / Q000737:chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000627:therapeutic use / Q000633:toxicity; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes / Q000627:therapeutic use* / Q000633:toxicity
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D002614:Chelating Agents; D000071858:Epithelial Cell Adhesion Molecule; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid