title: Bioluminescence imaging serves as a dynamic marker for guiding and assessing thermal treatment of cancer in a preclinical model.
abstract: BACKGROUND
  Bioluminescence has been harnessed as a dynamic imaging technique in research. This is a proof of principle study examining feasibility of using bioluminescent proteins as a marker to guide therapeutic ablation.
  
  
  METHODS
  Mesothelioma cancer cells (MSTO-Td) were transfected with a retroviral vector bearing firefly luciferase gene, plated in serial dilutions, and imaged to compare bioluminescence signal to cell number, determining threshold of bioluminescence detection. MSTO-Td cells were subjected to thermal treatment in a heated chamber; the bioluminescence signal and number of remaining live cancer cells were determined. Mice with MSTO-Td xenografts underwent electrocautery tumor ablation guided by bioluminescence imaging; bioluminescence signal and tumor size were monitored for 3 weeks.
  
  
  RESULTS
  MSTO-Td cells emitted a bright, clear, bioluminescence signal that amplified with the cell number (P < .001) and was detectable with as few as 10 cells in cell culture. Bioluminescence decreased in a dose-dependent fashion upon thermal treatment as temperature increased from 37 to 70 °C (P < .001) and as treatment duration increased from 5 to 20 min (P < .001). This correlated with the number of remaining live MSTO-Td cells (Pearson coefficient = 0.865; P < .001). In mice, the bioluminescence signal correlated with tumor size posttreatment and effectively guided the ablation procedure to completion, achieving 0 % tumor recurrence.
  
  
  CONCLUSIONS
  Bioluminescence imaging is a sensitive, real-time imaging approach; bioluminescence reporters such as firefly luciferase can assess and guide thermal treatment of cancer. This encourages research into bioluminescence imaging as a molecular technique with potential to target tumors via biomarkers and optimize thermal treatment procedures in a clinical setting.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Joyce T
authors.initials: JT
authors.lastname: Au
authors.forename: Lorena
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Inna
authors.initials: I
authors.lastname: Serganova
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D004564:Electrocoagulation; D006801:Humans; D006979:Hyperthermia, Induced; D049409:Luciferases, Firefly / Q000235:genetics; D008163:Luminescent Measurements; D008654:Mesothelioma / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D051379:Mice; D057054:Molecular Imaging; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009368:Neoplasm Transplantation; D017785:Photons; D059629:Signal-To-Noise Ratio; D014162:Transfection
chemical_list: D049409:Luciferases, Firefly