Anti-antibody enhancement of iodine-131 anti-CEA radioimmunodetection in experimental and clinical studies.

Imaging of tumors with radiolabeled antibodies, especially when located in the blood-rich visceral organs, may be improved through administration of a second antibody directed against the primary tumor-associated antibody. In hamsters bearing a human colonic carcinoma xenograft producing carcinoembryonic antigen (CEA), we injected donkey anti-goat IgG 24 hr after administration of 131I-labeled goat anti-CEA IgG and achieved enhanced tumor imaging 24-48 hr later, with a significant relative decrease of radioactivity in blood and all major organs except the spleen. In seven of nine patients, this method of anti-antibody clearance of nontargeted radioactive murine monoclonal antibodies revealed sites of cancer, including liver metastases. Characterization of radioactivity in the plasma before and after administration of the second antibody confirmed that complexes were quickly formed between primary and secondary antibodies, and imaging of the patients revealed a rapid uptake of radioactivity in the liver at 2 hr that dissipated within 24 hr. Radioactivity in the spleen gradually increased over time. The method of anti-antibody immunological enhancement of cancer imaging is feasible and may reveal tumor sites missed by conventional imaging.