title: Targeting CD44v6 expressed in head and neck squamous cell carcinoma: preclinical characterization of an 111In-labeled monoclonal antibody.
abstract: In patients with head and neck squamous cell carcinoma (HNSCC) radioimmunodiagnosis could offer a more specific and sensitive tumor diagnostic method. Our aim was to evaluate the labeling and biodistribution of the novel radioimmunoconjugate (111)In-cMAb U36. In this study cMAb U36, targeting CD44v6, and huA33, as a negative control, were labeled with indium-111, using the chelator CHXA''-DTPA. Immunoreactivity assays and binding studies were performed in vitro. Biodistribution and tumor imaging were conducted after intravenous injection of the radioimmunoconjugate to nude mice bearing HNSCC xenografts expressing CD44v6. The immunoreactive fraction was very high and the binding was CD44v6-specific. In vivo results demonstrated a promising biodistribution, with tumors clearly accumulating radioactivity with time. At 168 h postinjection (p.i.) the tumor uptake was 54.7 +/- 16.6% injected dose/g. The cMAb U36 had significantly (p < 0.05) higher uptake in tumors 72 h p.i. compared to huA33. We produced a novel radioimmunoconjugate targeting CD44v6 for possible use in the detection of HNSCC. The conjugate demonstrates no adverse effects from labeling and a favorable biodistribution.
authors.affiliation: Department of Surgical Sciences, Unit of Otolaryngology and Head & Neck Surgery, Uppsala University, Uppsala, Sweden. karl.sandstrom@surgsci.uu.se
authors.forename: Karl
authors.initials: K
authors.lastname: Sandström
authors.forename: Marika
authors.initials: M
authors.lastname: Nestor
authors.forename: Tomas
authors.initials: T
authors.lastname: Ekberg
authors.forename: Mats
authors.initials: M
authors.lastname: Engström
authors.forename: Matti
authors.initials: M
authors.lastname: Anniko
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009206:Myocardium / Q000276:immunology; D016719:Radioimmunodetection; D012680:Sensitivity and Specificity; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors; D007205:Indium Radioisotopes