title: Fractionated radioimmunotherapy with ⁹⁰Y-labeled fully human anti-CEA antibody.
abstract: Carcinoembryonic antigen (CEA) is an attractive target molecule of radioimmunotherapy (RIT). To enhance RIT's therapeutic efficacy, the fractionation of radiolabeled antibody doses is an attractive strategy. In this study, a fully human anti-CEA monoclonal antibody (mAb) C2-45 was selected by virtue of its lack of immunogenicity, and the effectiveness of fractionated RIT with yttrium-90 (⁹⁰Y)-labeled mAb C2-45 was evaluated. In LS180 tumor-bearing mice, indium-111 (¹¹¹In)-labeled mAb C2-45 showed high and persistent tumor accumulation. Therapeutic studies were performed with single doses of ⁹⁰Y-mAb C2-45 (100 or 200 μCi) or double doses of 100 μCi ⁹⁰Y-mAb C2-45 at different intervals (5, 10, and 15 days). All ⁹⁰Y-mAb C2-45-treated mice showed inhibition of tumor progression, while the time to tumor progression was much longer in both the 200-μCi-treated group and the double 100-μCi-treated group than in the single 100-μCi-treated group. The therapeutic effect of the double 100 μCi administration at days 0 and 15 lasted significantly longer than that in the other treatment groups. These findings indicate that ⁹⁰Y-mAb C2-45 may be a promising agent for the treatment of CEA-positive cancer and that the fractionation of ⁹⁰Y-labeled antibody doses could enhance the therapeutic effect if performed according to an appropriate protocol.
authors.affiliation: 1 Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Arifudin
authors.initials: A
authors.lastname: Achmad
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tsushima
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes