title: Radioimmunoscintigraphy using technetium-99m-labeled parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen in athymic nude mice bearing tumor.
abstract: Biodistribution and imaging characteristics of Tc-99m-labeled parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, were evaluated in athymic nude mice bearing the human CEA-producing gastric carcinoma (MKN-45) xenografts. Group F monoclonal antibodies such as F11-39 and ChF11-39 have been found to recognize the protein epitopes present on the domain B3 of the CEA molecule and to discriminate CEA in tumor tissues from the CEA-related antigens. The Tc-99m labeling was performed by immediately mixing a reduced antibody by 2-mercaptoethanol with Tc-99m pertechnetate in the presence of stannous chloride. The labeling yields of the two antibodies were greater than 95% when estimated using gel chromatography. Although these Tc-99m-labeled antibodies were stable in neutral saline solution, Tc-99m from both labeled antibodies was associated with cysteine solution. Technetium-99m ChF11-39 was more susceptible to transchelation than was Tc-99m F11-39. The immunoreactivity of each Tc-99m-labeled antibody was confirmed using MKN-45 cell-binding assay. Biodistribution studies in tumor-bearing mice were performed at 1 h, 5 h, and 20 h after being given IV injections of 3.7 MBq of either Tc-99m F11-39 or Tc-99m ChF11-39. All tumor-to-organ uptake ratios increased with time for both Tc-99m-labeled antibodies. Imaging results also showed selective and progressive accumulation of both Tc-99m antibodies at the tumor site. Both these Tc-99m-labeled antibodies have proved to be good radiotracers giving satisfactory scintigrams of the CEA-producing tumor.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Karube
authors.forename: K
authors.initials: K
authors.lastname: Katsuno
authors.forename: J
authors.initials: J
authors.lastname: Takata
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
authors.forename: M
authors.initials: M
authors.lastname: Haruno
authors.forename: M
authors.initials: M
authors.lastname: Kuroki
authors.forename: F
authors.initials: F
authors.lastname: Arakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: H
authors.initials: H
authors.lastname: Kanda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D017556:Technetium Compounds / Q000276:immunology / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D011993:Recombinant Fusion Proteins; D017556:Technetium Compounds