title: Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide.
abstract: BACKGROUND
  The effectiveness of near-infrared imaging (NIR) interrogation of epidermal growth factor receptor (EGFR) expression as a sensitive biomarker of oral squamous cell carcinoma (OSCC) response to arsenic trioxide therapy was studied in mice.
  
  
  METHODS
  A431 OSCC in vitro were exposed to 0 µM, 0.5 µM, 2.5 µM, or 5 µM of As(2)O(3) for 0 h, 24 h, 48 h and 72 h. Confocal microscopy and flow cytometry confirmed EGFR expression and demonstrated a sensitivity dose-related signal decline with As(2)O(3) treatment. Next, mice with pharynx-implanted A431 cells received As(2)O(3) i.p. every 48 h at 0.0, 0.5, 2.5, or 5 mg/kg/day (n = 6/group) from day 0 to 10. An intravenous NIR probe, EGF-Cy5.5, was injected at baseline and on days 4, 8, and 12 for dynamic NIR imaging. Tumor volume and body weights were measured three times weekly.
  
  
  RESULTS
  In vitro, A431 EGFR expression was well appreciated in the controls and decreased (p<0.05) with increasing As(2)O(3) dose and treatment duration. In vivo EGFR NIR tumor signal intensity decreased (p<0.05) in As(2)O(3) treated groups versus controls from days 4 to 12, consistent with increasing dosage. Tumor volume diminished in a dose-related manner while body weight was unaffected. Immunohistochemical staining of excised tumors confirmed that EGFR expression was reduced by As(2)O(3) treatment in a dose responsive pattern.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that OSCC can be interrogated in vivo by NIR molecular imaging of the EGFR and that this biomarker is effective for the longitudinal assessment of OSCC response to As(2)O(3) treatment.
authors.affiliation: Stomatology Department, Institute of Hard Tissue Development and Regeneration, 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Lingbo
authors.initials: L
authors.lastname: Zhang
authors.forename: Kezheng
authors.initials: K
authors.lastname: Wang
authors.forename: Falin
authors.initials: F
authors.lastname: Zhao
authors.forename: Weiping
authors.initials: W
authors.lastname: Hu
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002232:Carbocyanines; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D014408:Biomarkers, Tumor; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D010087:Oxides; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D000077237:Arsenic Trioxide