USE OF ANTICYTOKERATIN MONOCLONAL ANTIIDIOTYPIC ANTIBODIES TO IMPROVETUMOR NONTUMOR RATIO IN EXPERIMENTAL RADIOIMMUNOLOCALIZATION/

A syngeneic, high-affinity, anti-idiotypic monoclonal antibody (MAb; a lpha TS1) raised against an anticytokeratin monoclonal antibody (TS1) was evaluated as a second antibody to promote the rapid clearance of r adiolabeled TS1 from the blood during experimental radioimmunolocaliza tion, By using a novel biosensor technology (BIAcore), association rat e dissociation rate, and affinity constants between the idiotype and t he anti-idiotype could be determined, The in vivo results in nude mice carrying HeLa Hep 2 tumors demonstrate the possibility of selectively regulating the amount of the idiotypic I-125-labeled circulating MAb by in vivo injection of this high-affinity, anti-idiotypic antibody, I njection of the anti-idiotype in a molar ratio of 0.75 to the idiotype cleared the blood pool from circulating radiolabeled idiotype within 24 h, with a concomitant rapid excretion of I-125 in urine, The total amount of remaining radioactivity in the animals decreased to 15-20% d uring these 24 h, with the tumors still retaining 60-65% of their init ial radioactivity, This approach, using syngeneic primacy and secondar y MAbs with minimized immunogenicity, significantly improves the tumor :nontumor ratio, thus improving efficiency in experimental radioimmuno localization and radioimmunotherapy, leaving the endogenous antibody r epertoire of the host unaffected.