The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr after injection of the second antibody and to enhance tumor/nontumor ratios within 24 hr. Unlike liposomally entrapped second antibody, the primary anti-CEA antibody did not show increased accretion of radioactivity in the liver, spleen, or other major organs. These results suggest that administration of a second antibody alone may improve tumor imaging with a radiolabeled antitumor antibody.The concept of using radiolabeled antibodies to localize tumors in vivo was proposed three decades ago by Pressman and Korngold (1). However, only within the past 5 yr has this method, called radioimmunodetection (2), been found to be effective for imaging cancer by external scintigraphy (3-7). Although radioimmunodetection was relatively slow in development, there were several advances that enabled its clinical application. The development of high-titer antisera against tumor-associated antigens, such as carcinoembryonic antigen (CEA), and the refinement of techniques for specific antibody purification contributed toward improved radioimmunodetection of tumors (3,6). Initially, tumor imaging by external photoscanning could only be achieved several days after the injection of radiolabeled antibody because radioactivity in the circulation and nontarget tissues interfered with the delineation of tumor sites. In order to circumvent this problem, Goldenberg et al. (4) successfully used computer-assisted subtraction techniques to image primary and secondary tumor sites within 48 hr of injection of radiolabeled anti-CEA antibody. Other manipulations have been shown to enhance tumor imaging by radiolabeled antibodies in experimental animals models. Solter et al. (8) reported that F(ab')2 fragments were superior to whole antibody for tumor localization because the fragments were cleared more rapidly from the body than was whole IgG. Ryman and Barratt (9) and Begent et al. (10) showed that liposomally entrapped second antibody (LESA) directed against radioiodinated anti-tumor primary antibody accelerated the clearance of the radiolabeled antibody to 2-to 4-fold within 2 hr after administering LESA. Although accelerated clearance was observed from the blood within 2 hr, the radioactivity accumulated in the liver for 24 hr. The concentration of radioactivity in the liver can be attributed to the use of liposomes as a carrier for the second antibody because liposomes are known to accumulate in tissues rich in reticuloendothelial cells (9). The use of liposomes containing second antibody fosters other problems, such as inefficiency of incor...