title: Optical imaging predicts tumor response to anti-EGFR therapy.
abstract: To evaluate cetuximab treatment in head and neck squamous cell carcinoma xenografts and cell lines, we investigated a preclinical model of head and neck squamous cell carcinoma. Head and neck squamous cell carcinoma cell lines SCC-1, FaDu, CAL27, UM-SCC-5 and UM-SCC-22A were used to generate subcutaneous flank xenografts in SCID mice. Mice were divided into control and cetuximab treatment groups, mice in the latter group received 250 μg cetuximab once weekly for four weeks. After completion of therapy, SCC-1 (p < 0.001), UM-SCC-5 (p < 0.001), UM-SCC-22A (p = 0.016) and FaDu (p = 0.007) tumors were significantly smaller than control, while CAL27 tumors were not different from controls (p = 0.90). Mice were systemically injected with 50 μg of the Cy5.5-cetuximab bioconjugate and imaged by stereomicroscopy to determine if tumor fluorescence predicted tumor response. Intact tumor fluorescence did not predict response. Tissue was harvested from untreated xenografts to evaluate ex vivo imaging. Cell lines were then evaluated in vitro for fluorescence imaging after Cy5.5-cetuximab bioconjugate labeling. The location of fluorescence observed in labeled cells was significantly different for cell lines that responded to treatment, relative to unresponsive cells. Tumors from cell lines that showed low internalized signal in vitro responded best to treatment with cetuximab. This preclinical model may aid in determining which cancer patients are best suited for cetuximab therapy.
authors.affiliation: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Helman
authors.forename: J Robert
authors.initials: JR
authors.lastname: Newman
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Dean
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhang
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002232:Carbocyanines; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D018709:Statistics, Nonparametric; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D066246:ErbB Receptors; D000068818:Cetuximab