title: Introduction of five potentially metabolizable linking groups between 111In-cyclohexyl EDTA derivatives and F(ab')2 fragments of anti-carcinoembryonic antigen antibody--II. Comparative pharmacokinetics and biodistribution in human colorectal carcinoma-bearing nude mice.
abstract: The five linker-containing immunoconjugates described in the preceding paper were labeled with 111In and tested for their biodistribution, pharmacokinetics and immunoscintigraphic imaging properties in tumor-xenografted nude mice. The results were compared with DTPADA and CDTAMA for reference. Results showed that, for immunoscintigraphy, the derivatives in decreasing order of effectiveness were: aliphatic (tumor/liver > 4.5 and tumor/kidney > 6.5 at 96 h), thioether (tumor/liver > 3 and tumor/kidney > 1.2 at 24 h), ethylene glycol succinate (tumor/liver > 1.7 and tumor/kidney > 0.5 at 24 h) and disulfide (tumor/liver > 0.5 and tumor/kidney > 0.6 at 96 h). Pharmacokinetic results were complementary with those of the biodistribution studies and provide a basis for the study of in vivo metabolic mechanisms of linker-immunoconjugates. Indium-111-labeled linker-immunoconjugates appear promising for tumor imaging with better contrast than what is obtained with the use of the conventional 111In-DTPA dianhydride chelate.
authors.affiliation: INSERM Unit 211, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.forename: J F
authors.initials: JF
authors.lastname: Gestin
authors.forename: R C
authors.initials: RC
authors.lastname: Mease
authors.forename: C
authors.initials: C
authors.lastname: Sai-Maurel
authors.forename: P
authors.initials: P
authors.lastname: Thédrez
authors.forename: M
authors.initials: M
authors.lastname: Slinkin
authors.forename: G E
authors.initials: GE
authors.lastname: Meinken
authors.forename: S C
authors.initials: SC
authors.lastname: Srivastava
authors.forename: J F
authors.initials: JF
authors.lastname: Chatal
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D000906:Antibodies; D002272:Carcinoembryonic Antigen; D003432:Cross-Linking Reagents; D007205:Indium Radioisotopes; C005390:CDTA; D004492:Edetic Acid