High-dose,unlabeled, nonspecific antibody pretreatment: influence on specific antibody localization to human melanoma xenografts |
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Authors: | Richard L. Wahl Barry S. Wilson Monica Liebert William H. Beierwaltes |
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Affiliation: | (1) Division of Nuclear Medicine, University of Michigan Medical Center, 1500 East Medical Center Drive, 48109-0028 Ann Arbor, MI, USA;(2) Department of Pathology, Ann Arbor, Michigan, USA |
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Abstract: | Summary 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 isotypematched 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 g 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.Present address: Hybritech, San Diego, CA, USA |
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