Factors influencing anti-antibody enhancement of tumor targeting with antibodies in hamsters with human colonic tumor xenografts.

The injection of an antiantibody (second antibody, SA) can enhance the clearance rate of a radiolabeled antitumor antibody (primary antibody, PA) from the blood. We have studied how the dose of the SA and the timing of the SA administration influence the rate of PA clearance and thereby improve tumor/nontumor ratios. Adult hamsters bearing the carcinoembryonic antigen-producing, GW-39 human colonic tumor xenograft were given injections of 131I-labeled, goat anti-carcinoembryonic antigen antibody, and after 6, 24, or 48 h, an injection of donkey anti-goat immunoglobulin was given at SA:PA ratios of 25, 50, 100, or 200:1. In comparison to a control group of animals that were only given 131I-PA, the administration of the SA improved tumor/blood ratios regardless of the SA:PA ratio or time the SA was given. The most important factor in optimizing this procedure was the timing of the SA injection. Significantly improved tumor/nontumor ratios were found when the SA was given between 24 and 48 h after the PA in comparison to 6 h. This was because maximum accretion of radiolabeled PA in the tumor was not achieved until 24 h. At SA:PA ratios of 25:1, only tumor/blood ratios were significantly improved in comparison to the control group. In addition, at SA:PA ratios of 25:1 and 50:1, tumor/spleen and tumor/kidney ratios were lower than the control group, whereas at higher SA:PA ratios, all tumor/nontumor ratios were significantly improved. These studies suggest that for this model, a ratio of SA:PA of 100:1 or higher given at 24 to 48 h after the PA is the best combination for maximizing tumor/nontumor ratios.