Alpha v integrins as receptors for tumor targeting by circulating ligands.
Phage displaying an Arg-Gly-Asp (RGD)-containing peptide with a high affinity for alpha v integrins homed to tumors when injected intravenously into tumor-bearing mice. A substantially higher amount of alpha v-directed RGD phage than control phage was recovered from malignant melanomas and breast carcinoma. Antibodies detected the alpha v-directed RGD phage in tumor blood vessels, but not in several normal tissues. These results show that the alpha v integrins present in tumor blood vessels can bind circulating ligands and that RGD peptides selective for these integrins may be suitable tools in tumor targeting for diagnostic and therapeutic purposes.
Pasqualini
R
R
La Jolla Cancer Research Center, Burnham Institute, La Jolla, CA, USA. rarap@ljcrf.edu (RP); ruoslahti@ljcrf.edu (ER)
Koivunen
E
E
Ruoslahti
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001435:Bacteriophages; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D019030:Receptors, Vitronectin / Q000502:physiology*; D014183:Transplantation, Heterologous
D000956:Antigens, Viral; D004337:Drug Carriers; D009842:Oligopeptides; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid