title: Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.
abstract: OBJECTIVE
  Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC.
  
  
  OBJECTIVE
  To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia.
  
  
  METHODS
  This was an observational study (including sensitivity and specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches.
  
  
  METHODS
  Various HNSCC xenografts were established in the tongues of NOD-scid IL2Rgammanull (NSG) mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the cheek pouch of Golden Syrian hamsters for 9 to16 weeks. BLZ-100 was subcutaneously injected, and fluorescence uptake was measured.
  
  
  METHODS
  The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades.
  
  
  RESULTS
  In HNSCC xenografts, BLZ-100 demonstrated a mean (SD) SBR of 2.51 (0.47). The ROC curve demonstrated an area under the curve (AUC) of 0.89; an SBR of 2.50 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and nontumor interface, the AUC increased to 0.97; an SBR of 2.50 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 [0.71] vs 1.51 [0.34], P = .006).
  
  
  CONCLUSIONS
  BLZ-100 is a sensitive and specific marker of HNSCC and can distinguish high-risk from low-risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of premalignant lesions.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle.
authors.forename: Fred M
authors.initials: FM
authors.lastname: Baik
authors.affiliation: Blaze Bioscience Inc, Seattle, Washington.
authors.forename: Stacey
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus.
authors.forename: Sue E
authors.initials: SE
authors.lastname: Knoblaugh
authors.affiliation: Blaze Bioscience Inc, Seattle, Washington.
authors.forename: Disha
authors.initials: D
authors.lastname: Sahetya
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Mitchell
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
authors.affiliation: Blaze Bioscience Inc, Seattle, Washington.
authors.forename: Julia
authors.initials: J
authors.lastname: Parrish-Novak
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle4Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Méndez
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007208:Indocyanine Green / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008647:Mesocricetus; D051379:Mice; D016688:Mice, Inbred NOD; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009374:Neoplasms, Experimental; D012372:ROC Curve; D012604:Scorpion Venoms / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014059:Tongue / Q000473:pathology*
chemical_list: D004396:Coloring Agents; D007457:Iodine Radioisotopes; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000604732:tozuleristide; D007208:Indocyanine Green