Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

Myelotoxicity is the main factor which decides the maximum tolerated dose ( MTD) in radioimmunotherapy (RIT), Since bone marrow is mostly irradiated fr om blood radioactivity, enhancing the clearance of unbound circulating radi olabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high t umor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therape utic outcome, Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated (131 )-labeled anti-CEA monoclonal antibody (MAB) (24-38 mu g, 11.1 mBq). Mice o f the chase group then received an intravenous injection of avidin twice (2 4 and 30 h, 72-115 mu g each), Biodistribution, side effects (white blood c ell counts and body weight change), and short- and long-term therapeutic ef fects were determined. Avidin chase markedly accelerated the clearance of r adiolabeled MAb from the blood (P < 0.0001) and normal tissues? resulting i n milder leukocytopenia and body weight loss, both of which recovered earli er than in the non-chase group (P < 0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background r atios were increased. Avidin chase gave the therapeutic gain ratio of 1.89, Treated groups with and without avidin chase showed significant therapeuti c effects compared to the non-treated group, There was no significant diffe rence in the therapeutic effects between the two treated groups, Avidin cha se effectively reduced the side effects of RIT and should increase the MTD.