title: Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9.
abstract: Although metastatic rhabdomyosarcoma (RMS) is chemotherapy and radiotherapy responsive, few patients are cured. 8H9, a murine IgG(1) monoclonal antibody, recognizes a unique cell surface tumor antigen broadly distributed on neuroectodermal, epithelial, and mesenchymal tumors, including RMS. We now report on the in vitro characterization of radiolabeled 8H9 and its in vivo immunotargeting potential in mice with subcutaneous human RMS. Saturation-binding studies carried out to determine (125)I-8H9 affinity to the RMS cell line HTB82 demonstrated that (125)I-8H9 had a K(d) of 10.3nM with an estimated 115,000 binding sites on every HTB82 cell. (125)I-8H9 was retained on the cell surface without significant internalization. Biodistribution of (125)I-8H9 was studied in athymic mice bearing HTB82 xenografts. Following intravenous injection of 4.44MBq of (125)I-8H9, selective tumor uptake was evident 4 to 172 hours after injection. Average tumor uptake was 7.0 +/- 1.8, 11.5 +/- 3.9, 15.1 +/- 3.7, and 5.4 +/- 1.2% injected dose per gram at 4, 24, 48, and 172 hours, respectively. Mean tumor: tissue ratios were maximal at 172 hours (for lung, 4, kidney, 6, liver, 7, spleen, 11, femur, 14, muscle, 18, and brain, 48). Established RMS xenografts treated with a single injection of 18.5 MBq (131)I-8H9 were significantly suppressed compared to controls. Radiolabeled 8H9 effectively targeted RMS xenografts and may have a potential clinical role in radioimmunotherapy.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. modaks@mskcc.org
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Hong Fen
authors.initials: HF
authors.lastname: Guo
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018288:Carcinoma, Small Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D007700:Kinetics; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011485:Protein Binding; D016499:Radioimmunotherapy / Q000379:methods*; D012208:Rhabdomyosarcoma / Q000628:therapy*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C507846:8H9 monoclonal antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes