High-dose, unlabeled, nonspecific antibody pretreatment: influence on specific antibody localization to human melanoma xenografts.
Nonspecific uptake of radiolabeled monoclonal antibodies in normal tissues is a significant problem for tumor imaging. A potential means of decreasing nonspecific antibody binding is to "blockade" nonspecific antibody binding sites by predosing with cold, nonspecific isotype-matched antibody, before injecting specific antibody. Nontumor-specific murine monoclonal antibody LK2H10 (IgG1) or Ab-1 (IgG2a) was given i.v. at doses of 0 to 3.5 mg to nude mice with xenografts of human melanoma. These mice were then given i.v. 4 micrograms of 131I anti-high molecular weight antigen of melanoma (HMWMAA) monoclonal antibody 763.24T (IgG1) or 225.28S (IgG2a), respectively. These mice were also given a tracer dose of 125I LK2H10 or Ab-1, respectively. Specific tumor uptake of anti-HMWMAA antibodies was see in all cases. No drop in tumor or nontumor uptake was demonstrated for either of the tumor-specific or nonspecific monoclonal antibodies due to nonspecific monoclonal antibody pretreatment. These data suggest that high doses of isotype-matched unlabeled nonspecific monoclonal antibody given before 131I tumor-specific monoclonal antibody, will not enhance tumor imaging.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000008:administration & dosage / Q000378:metabolism; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D009368:Neoplasm Transplantation; D011961:Receptors, Fc / Q000378:metabolism; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc