Biodistribution of 131I-labeled Anti-CK8 Monoclonal Antibody in HNSCC in Xenotransplanted SCID Mice

• Published in: Anticancer research Vol. 31; no. 10; pp. 3315 - 3321
• Main Authors: ANDRATSCHKE, Michaela, LUEBBERS, Christian W, JOHANNSON, Veronika, SCHMITT, Baerbel, MACK, Brigitte, ZEIDLER, Reinhard, LANG, Stephan, WOLLENBERG, Barbara, GILDEHAUS, Franz Josef
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.10.2011
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - pharmacokinetics; Antigens, Neoplasm - immunology; Biological and medical sciences; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Head and Neck Neoplasms - blood; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Humans; Immunohistochemistry; Injections, Intravenous; Iodine Radioisotopes - administration & dosage; Iodine Radioisotopes - blood; Iodine Radioisotopes - pharmacokinetics; Isotope Labeling; Keratin-8 - immunology; Maximum Tolerated Dose; Medical sciences; Mice; Mice, SCID; Organ Specificity; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Squamous Cell Carcinoma of Head and Neck; Tissue Distribution; Transplantation, Heterologous; Tumors; Xenograft Model Antitumor Assays; Cytokeratin; Animal model; xenografts; Transplantation; Monoclonal antibody; Radioisotope; Heterotransplantation; radio-labeled monoclonal antibody; Cancerology; Surgery; SCID mice; Immunoradiotherapy; Graft; ENT disease; Head and neck squamous cell carcinoma; Cytokeratin 8; Sodium iodide (131I); Radioimmunotherapy; Severe combined immunodeficient mouse; Malignant tumor; Radiotherapy; Treatment; Animal; HNSCC; Cancer
• ISSN: 0250-7005; 1791-7530

A new promising approach to improve the outcome of head and neck squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate filament forming protein, is shown to be de novo expressed in dysplastic lesions as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8 seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to investigate the biodistribution of a radio-labeled Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined immunodeficiency disease) mouse model. The mAb against CK8 was labeled with (131)I and biodistribution was tested in established HNSCC xenografts in SCID mice. The biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. Initially, after systemic administration of (131)I-anti CK8 monoclonal antibody high activity was seen in all the organs. Over time the general activity decreased, whereas activity accumulated in the tumor. This activity decayed compared to the other tissues with a two- to threefold prolonged radioactive half-life. Specific antibody-antigen-binding is probably responsible for the prolonged radioactive half-life in the tumor and the resulting cumulative activity due to enrichment of the (131)I-anti CK8 mAb, so that Cytokeratin 8 seems to be a suitable anchor molecule for radioimmunotherapy in HNSCC.