title: Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody.
abstract: The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49DeltaCH2) to be utilized in a radioimmunotherapeutic (RIT) application with 213Bi. An initial study indicated that 111In-HuCC49DeltaCH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49DeltaCH2 was then radiolabeled with 213Bi, an alpha-emitting radionuclide with a half-life of 45.6 minutes, and evaluated for therapeutic efficacy. Dose titration studies indicated that a single dose of 500-1000 microCi, when injected by an intraperitoneal route, resulted in the growth inhibition or regression of the tumor xenograft. The radioimmunotherapeutic effect was found to be dose-dependent. Specificity of the therapeutic efficacy was confirmed in a subsequent experiment with athymic mice bearing TAG-72 negative MIP (human colorectal) xenografts. A preliminary study was also performed to assess a multiple-dose administration of 213Bi-HuCC49DeltaCH2. Doses (500 microCi) were administered at 14-day intervals after tumor implantation. A reduction in volume and/or delay in tumor growth was evident following the second and third injections of 213Bi-HuCC49DeltaCH2. As further validation of the use of 213Bi-HuCC49DeltaCH2 for RIT, a study using 131I was conducted. The overall survival of mice receiving 213Bi-HuCC49DeltaCH2 was greater than those that received 131I-HuCC49DeltaCH2.
authors.affiliation: Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Milenic
authors.forename: Kayhan
authors.initials: K
authors.lastname: Garmestani
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
authors.forename: Lara
authors.initials: L
authors.lastname: Chappell
authors.forename: Paul
authors.initials: P
authors.lastname: Albert
authors.forename: Donald
authors.initials: D
authors.lastname: Hill
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Martin
authors.initials: M
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001729:Bismuth / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D016019:Survival Analysis; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D001729:Bismuth