Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of iodine-125-labeled BR96-biotin monoclonal antibody.

Abstract

This study investigates the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody using a new method, whole-blood immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal antibody (MAb) from blood without preceding separation of plasma. Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian male rats were inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after injection. About six blood volumes were passed through an avidin-gel adsorption column during 2 hr. By using WBIA, whole-body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 hr later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p > 0.05) and had approximately similar time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to 30:1. This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.