EXTRACORPOREAL WHOLE-BLOOD IMMUNOADSORPTION ENHANCES RADIOIMMUNOTARGETING OF IODINE-125-LABELED BR96-BIOTIN MONOCLONAL-ANTIBODY

This study investigates the efficacy of tumor radioimmunotargeting wit h I-125-labeled BR96-biotin monoclonal antibody using a new method, wh ole-blood immunoadsorption (WBIA), based on direct adsorption of unbou nd monoclonal antibody (MAb) from blood without preceding separation o f plasma. Methods: Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) ce ll surface antigen. Forty-six Brown Norwegian male rats were inoculate d intramuscularly and beneath the liver or kidney capsule with syngene ic rat colon carcinoma BN7005, expressing Lewis-type antigen, and inve stigated. The rats were injected intravenously with 3.5-4.5 MBq I-125- labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 1 2 hr after injection. About six blood volumes were passed through an a vidin-gd adsorption column during 2 hr. Results: By using WBIA, whole- body radioactivity was reduced by 50%, and plasma activity by 85%. Bot h directly after completion of WBIA and 33 hr later, the activity upta ke in tumors manifested only a nonsignificant decrease as compared wit h 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 mo dels, as compared with controls. The ratio of liver tumor to bone marr ow was improved from 10:1 to 30:1. Conclusion: This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-re active, internalizing MAb BR96.