Bioluminescence imaging serves as a dynamic marker for guiding and assessing thermal treatment of cancer in a preclinical model

Ann Surg Oncol. 2012 Sep;19(9):3116-22. doi: 10.1245/s10434-012-2313-7. Epub 2012 Mar 31.

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.

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Line, Tumor
  • Electrocoagulation
  • Humans
  • Hyperthermia, Induced
  • Luciferases, Firefly / genetics
  • Luminescent Measurements*
  • Mesothelioma / genetics
  • Mesothelioma / pathology
  • Mesothelioma / surgery*
  • Mice
  • Molecular Imaging*
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Transplantation
  • Photons
  • Signal-To-Noise Ratio
  • Transfection

Substances

  • Luciferases, Firefly