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.
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Acknowledgment
The authors would like to thank Susanne Carpenter, Joshua Carson, Dana Haddad, Arjun Mittra, Valerie Longo, and Pat Zanzonico for their advice and support of this work.
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Au, J.T., Gonzalez, L., Chen, CH. et al. Bioluminescence Imaging Serves as a Dynamic Marker for Guiding and Assessing Thermal Treatment of Cancer in a Preclinical Model. Ann Surg Oncol 19, 3116–3122 (2012). https://doi.org/10.1245/s10434-012-2313-7
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DOI: https://doi.org/10.1245/s10434-012-2313-7