Comparative tumour localization of antibody fragments and intact IgG in nude mice bearing a CEA-producing human colon tumour xenograft.
The dynamics of distribution of radiolabelled F(ab')2 fragments of a monoclonal anti-CEA antibody have been studied in the nude mouse bearing a CEA-producing human colon carcinoma. Our results showed that the fragment was rapidly cleared from all normal organs reaching about 1% of that injected by 24 hr. Specific tumour localization occurred as early as 2 hr after injection and was complete by 4 hr. The amount of fragment localized in tumour was 4% of the injected dose, equivalent to that obtained with the intact antibody. Greatly improved tumour:normal tissue ratios were obtained with the fragment compared to intact IgG. However, the residence time of the fragment was much shorter (24 hr) than that of intact antibody (more than 3 days). Tumour localization indices suggested that fragments were superior to intact IgG at locating tumour specifically. The specificity indices based on lung, spleen and liver were much higher than those for intact antibody, reflecting the lack of Fc-receptor binding of fragments and their reduced excretion by these organs. The 'fragment index' enabled tumour:normal tissue ratios for the fragment and intact IgG to be compared. Together with the distribution study at different time points, this simplifies the task of defining a 'time window' in which tumour imaging and therapy might be optimal.
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis*; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G