DIFFERENCES IN BIODISTRIBUTION OF THE ANTI-(CARCINOEMBRYONIC ANTIGEN)MURINE MONOCLONAL-ANTIBODY-CE-25, ITS F(AB')(2)-FRAGMENT AND ITS INTACT MAINLY HUMAN CHIMERIC FORM CE-4-8-23 - DEPENDENCE ON TUMOR SIZE ANDAMOUNT OF ANTIBODY INJECTED

The effect of the size of the tumour and the amount of antibody inject ed on the biodistribution of a family of radioiodinated antibodies was studied. The intact mouse anti-(carcinoembryonic antigen) (anti-CEA) monoclonal antibody CE-25, its F(ab')(2) fragment and the intact human -mouse chimeric from CE 4-8-13 were evaluated in a model system using the human CEA-producing colon xenograft T 380 grown in nude mice. The relative retention (the percentage of the injected dose per gram of ti ssue), of mouse mAb and F(ab')(2) in tumour and most normal tissues 1 day after injection was independent of the antibody dose; after 4 days the mAb values increased with increasing antibody dose. The relative retention of chimeric mAb increased with increasing antibody dose 1 da y after injection and also slightly after 4 days. The relative retenti on in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from d ay 1 to day 4; for chimeric mAb this value decreased. In normal tissue s the relative retention of mouse mAb decreased from day 1 to day 4, b ut the relative retention of chimeric mAb in normal tissue dropped rap idly and changed little afterwards. Thus the biokinetics of antibodies is ''species''-dependent: foreign, mainly human, chimeric antibody cl ears faster from normal mouse tissue than mouse antibody and reaches l ower concentrations.