[Experimental study of the relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled anti-CEA monoclonal antibodies].
The immunoreactivity and affinity of seven kinds of monoclonal antibody raised against human gastric cancer (MKN-45) secreted carcinoembryonic antigen (CEA) were determined with the method of cell binding assay in vitro. Tumor localization and biodistribution of radiolabeled antibodies were performed in athymic mice implanted MKN-45 xenografts. Results obtained were as follows: 1) The affinity constant of CEA-specific three antibodies (1A4, 1B2, 4H11) was the same approximately, whereas the immunoreactivity found to be quite different among them. While CEA-nonspecific four antibodies (7D1, 6C7, 2C3, 5H7) showed the much higher affinity constant than that of the former. 2) In an animal model on tumor localization and biodistribution studies, CEA-specific antibodies obtained more highly tumor targeting and cleared more rapidly from the blood and non-tumor organs than CEA-nonspecific antibodies did, so that tumor to nontumor ratios was increased. 3) In this model system it is the immunoreactivity preparation of antibodies that improved tumor targeting and tumor activity retention, on the other side, the affinity constant of antibodies were associated with rapid clearance from the blood and non tumor sites. In conclusion, this studies would also be beneficial for practical use and clinical application of radiolabeled monoclonal antibodies.
Takeda
A
A
Second Department of Surgery, School of Medicine, Chiba University.
Miyoshi
T
T
Arimizu
N
N
Isono
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000493:pharmacokinetics; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes