title: Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery.
abstract: Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non-specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross-linking of reduced Fab' fragments from PR1A3 and T84.66. Fifty-nine tumors from 2 human colorectal carcinoma cell lines with high (KM-12c) and low (Clone A) carcinoembryonic antigen (CEA) expression were successfully implanted subcutaneously on the backs of 42 nude mice. Tumors were localized using 125I-labeled MAbs: IgG, F(ab')(2) and Fab' of PR1A3, and biparatopic MAb of PR1A3 and T84.66. Radioactivity counted on a portable radioisotope detector correlated well with that counted on a gamma counter (p < 0.001). Accumulations of radioactivity in control mice without tumorigenesis were the greatest in PR1A3 IgG-pretreated mice and the least in biparatopic MAb-pretreated mice. Tumors of 2 cell lines did not differ in the distribution of radiolabeled MAbs. Localization indices of the tumor in various organs revealed 1.3 to 4.1 in PR1A3 IgG-pretreated mice, 2.4 to 6.6 in fragment MAbs of PR1A3-pretreated mice and 2 to 4.6 in biparatopic MAb-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells of all types of MAb-pretreated mice. Sensitivity and specificity of tumor localization by radioimmunoguided surgery (RIGS) were the highest in the biparatopic MAb-pretreated mice (90.9% and 94.5%, respectively) and the least in the PR1A3 IgG-pretreated mice (50% and 72%). The biparatopic MAb using 2 anti-CEA MAbs against different epitopes achieved a great affinity and avidity with accurate localization of colorectal carcinoma in experimental radioimmunoguided surgery.
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Seoul, Korea. jckim@www.amc.seoul.kr
authors.forename: Jin C
authors.initials: JC
authors.lastname: Kim
authors.forename: Seon A
authors.initials: SA
authors.lastname: Roh
authors.forename: Kum H
authors.initials: KH
authors.lastname: Koo
authors.forename: Jang H
authors.initials: JH
authors.lastname: Ryu
authors.forename: Hyun K
authors.initials: HK
authors.lastname: Hong
authors.forename: Seung J
authors.initials: SJ
authors.lastname: Oh
authors.forename: Jin S
authors.initials: JS
authors.lastname: Ryu
authors.forename: Ho J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Walter F
authors.initials: WF
authors.lastname: Bodmer
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D000939:Epitopes / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D017434:Protein Structure, Tertiary; D016719:Radioimmunodetection; D011874:Radiometry / Q000295:instrumentation; D012680:Sensitivity and Specificity; D025321:Surgery, Computer-Assisted; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D013667:Technetium