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 4-8-13. Dependence on tumour size and amount of antibody injected.
The effect of the size of the tumour and the amount of antibody injected 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 tissue), 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 day after injection and also slightly after 4 days. The relative retention in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from day 1 to day 4; for chimeric mAb this value decreased. In normal tissues the relative retention of mouse mAb decreased from day 1 to day 4, but the relative retention of chimeric mAb in normal tissue dropped rapidly and changed little afterwards. Thus the biokinetics of antibodies is "species"-dependent: foreign, mainly human, chimeric antibody clears faster from normal mouse tissue than mouse antibody and reaches lower concentrations.
Westera
G
G
Department of Radiology, University Hospital, Zürich, Switzerland.
Rülicke
T
T
Smith
A
A
Duewell
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins