Biodistribution of monoclonal antibody Po66 in a human lung tumour-bearing mouse model: effect of blood exchange on tumour antibody uptake.
We report a method designed to improve the specificity of tumour uptake after intravenous injection of an anti-tumour monoclonal antibody (MAb). It consists in increasing the blood clearance of the MAb injected in order to diminish its tissue activity, without altering tumour binding. Po66, an MAb directed against lung squamous cell carcinoma, was radiolabelled with 125I and injected i.v. into tumour-bearing nude mice. Radioactivity uptake by the tumour reached a plateau on days 3-5 which persisted up to day 14 after antibody injection. The radiolabelled Po66 remaining in the circulation on day 5 after injection was removed by means of exsanguination and blood transfusion. This blood exchange technique depleted circulating radiolabelled MAb by 60%, whenever mice had been injected with Po66 or an unrelated control IgG1. The proportion of radiolabelled Po66 taken up by the tumour 5 days after blood exchange did not differ substantially from that of non-exsanguinated controls (96.1% of controls). In contrast, there was a significant decrease in blood radioactivity (46% of control values on day 5). Blood exchange provoked a 1.8 fold increase in the tumour/blood and a 1.5-1.8 fold increase of the tumour/organ radioactivity ratios. After injection of unrelated radiolabelled IgG1, blood exchange reduced by 50% both blood and tumour radioactivity, and did not increase the tumour/blood or tumour/organ ratios. Hence, removal of 60% of circulating Po66, 5 days after its injection, did not affect the binding or retention of the antibody by the tumour, but would probably constitute a marked improvement if the antibody is used for two-phase radioimmunotherapy.
Desrues
B
B
Service de Pneumologie, Centre Hospitalier Regional et Universitaire, Hôpital Pontchaillou, Rennes, France.
Quinquenel
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ML
Toujas
L
L
Delaval
P
P
Dazord
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D017690:Cell Transplantation / Q000502:physiology; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000502:physiology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes