Influence of animal host and tumor implantation site on radio-antibody uptake in the GW-39 human colonic cancer xenograft.
The magnitude and kinetics of tumor uptake of a monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA) in the GW-39 human colorectal cancer xenograft differ according to the animal used (nude mouse or hamster) and the site of implantation of the tumor within the animal (cheek pouch, leg muscle, subcutaneous or liver). Several physiological factors have been evaluated in an attempt to explain these differences in radio-antibody accumulation. The following observations have been made: (1) The animal host with the slower blood clearance of radio-antibody and the higher non-tumor tissue uptake has the higher tumor uptake; (2) the xenografts with a higher blood-flow rate, vascular volume and/or vascular permeability have a higher specific radio-antibody targeting; (3) the smaller, more viable tumors take up more radio-antibody per gram than the larger tumors; and (4) tumors with higher specific antigen content accrete more radio-antibody. These results are discussed in terms of the feasibility of clinical tumor imaging and therapy with radiolabelled antibodies.
Blumenthal
R D
RD
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry, Newark, NJ 07103.
Sharkey
R M
RM
Kashi
R
R
Natale
A M
AM
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000493:pharmacokinetics; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013045:Species Specificity; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen