title: Tumor targeting and pharmacokinetics of unmodified and modified F(ab)2 fragments of an anti-CEA murine monoclonal antibody (Immu-14).
abstract: Pharmacokinetic studies were performed with two different 111In-labeled F(ab)2 fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-14). Unmodified F(ab)2 and modified Fab-BMH-Fab fragments were compared in nude mice bearing a LS-174T human colon carcinoma tumor xenograft. Tumor accumulation is significantly higher for modified fragments than for unmodified fragments at all time points. At 24 h post injection, tumor uptake for modified and unmodified fragments reached 40 and 25% ID g, respectively. The retention of radioactivity in the liver was approx. 2-fold higher for modified fragments. Kidney uptake of modified fragments was at least 2-fold lower than that of unmodified fragments. Although blood radioactivity decreased rapidly for both fragments, the cumulative tumor activity was 40% higher for Fab-BMH-Fab fragment. Modified F(ab)2 fragments can deliver higher radiation doses to the tumor.
authors.affiliation: Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030-4095, USA.
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
authors.forename: S M
authors.initials: SM
authors.lastname: Quadri
authors.forename: G L
authors.initials: GL
authors.lastname: Griffiths
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: H M
authors.initials: HM
authors.lastname: Vriesendorp
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice / Q000276:immunology; D008819:Mice, Nude; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes