title: Detection of oral squamous cell carcinoma and cervical lymph node metastasis using activatable near-infrared fluorescence agents.
abstract: OBJECTIVE
  To assess the feasibility of optical imaging using activatable near-infrared fluorescence (NIRF) agents to detect oral cancer and cervical lymph node metastasis in vivo.
  
  
  METHODS
  In vivo study.
  
  
  METHODS
  University medical center.
  
  
  METHODS
  Female nude mice aged 4 to 6 weeks.
  
  
  METHODS
  Luciferase-expressing OSC-19-luc cells were injected into the tongues of nude mice. A control group of nude mice was injected in the tongue with a physiologic saline solution. Tumor growth was followed by bioluminescence imaging. After 3 weeks, animals were randomly allocated to intravenous administration of 1 of 2 activatable NIRF agents: ProSense680 or MMPSense680. Fluorescence imaging of the mice was performed, and the tumor to background ratio (TBR) was determined on histologic sections of the tongue and cervical lymph nodes after resection at necropsy.
  
  
  METHODS
  Fluorescence signals.
  
  
  RESULTS
  The fluorescence signals in tongue tumor and cervical lymph node metastases were significantly higher than those in control animals. The mean (SD) TBR of ProSense680 in the tongue was 15.8 (8.1) and in the lymph nodes was 11.8 (3.6). For MMPSense680, the mean (SD) TBR in the tongue was 18.6 (9.4) and in the lymph nodes was 10.5 (4.0).
  
  
  CONCLUSIONS
  Oral cancer and cervical lymph node metastases can be detected by targeting increased proteolytic activity at the tumor borders using NIRF optical imaging. These NIRF agents could be used for real-time image-guided surgery, which has the potential to improve the complete surgical resection of oral cancer.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. s.keereweer@erasmusmc.nl
authors.forename: Stijn
authors.initials: S
authors.lastname: Keereweer
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Mol
authors.forename: Pieter B A A
authors.initials: PB
authors.lastname: Van Driel
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Snoeks
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
authors.forename: Jeroen D F
authors.initials: JD
authors.lastname: Kerrebijn
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D005453:Fluorescence; D008156:Luciferases; D049408:Luminescent Agents; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D011897:Random Allocation; D019265:Spectroscopy, Near-Infrared; D014062:Tongue Neoplasms / Q000473:pathology*; D014162:Transfection
chemical_list: D049408:Luminescent Agents; D008156:Luciferases