Quantitative evaluation of the localization of a monoclonal antibody (791T/36) in human osteogenic sarcoma xenografts.

Monoclonal antibody 791T /36 (IgG2b) directed against human osteogenic sarcoma-associated antigens has been used to examine quantitative aspects of in vivo tumour localization into osteogenic sarcoma xenografts. With small doses of antibody (less than 40 micrograms) the extent of localization consistently correlated with xenograft size, an average of 36% of the total body burden of radiolabelled antibody being present/g tumour after 2 or 3 days. Parallel studies with labelled control IgG2b showed a similar correlation, but only 7% of the total body radiolabel was localized/g tumour. With the 791T /36 antibody, the tumour: blood ratio did not increase with tumour size except with the largest xenografts (800-900 mg), where up to 30-40% of the total body radioactivity was localized within the xenografts and this was sufficient to produce a measurable decrease in its blood level. There was also a significant correlation between the dose of injected radiolabelled antibody and the amount localized in xenografts but only up to a dose of about 100 micrograms, beyond which the amount localized was not directly proportional to the injected dose. The maximum level of radiolabelled antibody localized in xenografts was 70 micrograms antibody/g tumour tissue. It was not possible to displace radiolabelled antibody already localized in xenografts by systemic administration of a large dose of unlabelled antibody. The rate of localization of antibody was such that maximum uptake, measured as the absolute amount of localized antibody, was seen 2-4 days after injection. After this time the absolute amount of antibody in the tumours declined, but not as rapidly as the blood and whole body levels, so that the tumour: blood ratio continued to increase with time.