Blood and tissue kinetics of radiolabelled anti-CEA monoclonal antibody and F(ab)2 and Fab fragments in nude mice with human tumour xenografts: implications for tumour imaging and radioimmunotherapy.
The kinetics of a radiolabelled anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments have been examined in mice including those with human tumour xenografts reactive with this antibody. With intact antibody the blood alpha phase half time was 9.9 h, the beta catabolic phase 128 h, with 55% of the remaining antibody in the intravascular compartment. Tumour localization was slow, peak levels of 22% of the dose g-1 being attained by 24 h, but remaining constant to at least 48 h. F(ab)2 fragments alpha and beta half times were 2.95 and 7.8 h, with an intravascular fraction of only 11%. Peak levels of tumour localization were seen within 7 h of injection but reached only 10% of the dose g-1 and then declined. Fab fragment half times were only 0.31 and 5.4 h, with 9% remaining intravascularly. Tumour localization was seen early but at only 2.5% of the dose g-1, and then declined. Tumour to blood ratios increased over time with all preparations, but reached only 2.5:1 with intact antibody compared with 15:1 and 19:1 with F(ab)2 and Fab respectively. These studies emphasize that the improved tumour: normal tissue ratios obtained with antibody fragments are the result of both faster and greater extravasation of fragments and their faster overall catabolism.
Pimm
M V
MV
Cancer Research Campaign Laboratories, University of Nottingham, UK.
Andrew
S M
SM
Baldwin
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments