Bioluminescence Imaging Serves as a Dynamic Marker for Guiding and Assessing Thermal Treatment of Cancer in a Preclinical Model
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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.
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.
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.
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.
- Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. AJR Am J Roentgenol. 2000;174:323–31.
- Lau WY, Leung TW, Yu SC, Ho SK. Percutaneous local ablative therapy for hepatocellular carcinoma: a review and look into the future. Ann Surg. 2003;237:171–9.
- Timmerman RD, Bizekis CS, Pass HI, Fong Y, Dupuy DE, Dawson LA, et al. Local surgical, ablative, and radiation treatment of metastases. CA Cancer J Clin. 2009;59:145–70. CrossRef
- de Wet JR, Wood KV, Helinski DR, DeLuca M. Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proc Natl Acad Sci USA. 1985;82:7870–3. CrossRef
- Dothager RS, Flentie K, Moss B, Pan MH, Kesarwala A, Piwnica-Worms D. Advances in bioluminescence imaging of live animal models. Curr Opin Biotechnol. 2009;20:45–53. CrossRef
- Serganova I, Moroz E, Vider J, Gogiberidze G, Moroz M, Pillarsetty N, et al. Multimodality imaging of TGFbeta signaling in breast cancer metastases. FASEB J. 2009;23:2662–72. CrossRef
- Silberhumer GR, Brader P, Wong J, Serganova IS, Gönen M, Gonzalez SJ, et al. Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma. Mol Cancer Ther. 2010;9:2761–9. CrossRef
- El Hilali N, Rubio N, Martinez-Villacampa M, Blanco J. Combined noninvasive imaging and luminometric quantification of luciferase-labeled human prostate tumors and metastases. Lab Invest. 2002;82:1563–71.
- Klerk CP, Overmeer RM, Niers TM, Versteeg HH, Richel DJ, Buckle T, et al. Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals. Biotechniques. 2007;43:7–13, 30.
- Sweeney TJ, Mailander V, Tucker AA, Olomu AB, Zhang W, Cao Y, et al. Visualizing the kinetics of tumor-cell clearance in living animals. Proc Natl Acad Sci USA. 1999;96:12044–9. CrossRef
- Troy T, Jekic-McMullen D, Sambucetti L, Rice B. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging. 2004;3:9–23. CrossRef
- Edinger M, Sweeney TJ, Tucker AA, Olomu AB, Negrin RS, Contag CH. Noninvasive assessment of tumor cell proliferation in animal models. Neoplasia. 1999;1:303–10. CrossRef
- Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, et al. Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol. 2002;160:1143–53. CrossRef
- Brader P, Stritzker J, Riedl CC, Zanzonico P, Cai S, Burnazi EM, et al. Escherichia coli Nissle 1917 facilitates tumor detection by positron emission tomography and optical imaging. Clin Cancer Res. 2008;14:2295–302. CrossRef
- Kelly KJ, Brader P, Woo Y, Li S, Chen N, Yu YA, et al. Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model. Int J Cancer. 2009;124:911–8. CrossRef
- Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, et al. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 2005;115:44–55.
- Goldman SJ, Chen E, Taylor R, Zhang S, Petrosky W, Reiss M, et al. Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice. PLoS One. 2011;6:e18269. CrossRef
- Lyons SK, Lim E, Clermont AO, Dusich J, Zhu L, Campbell KD, et al. Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer Res. 2006;66:4701–7. CrossRef
- Edinger M, Cao YA, Verneris MR, Bachmann MH, Contag CH, Negrin RS, et al. Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood. 2003;101:640–8. CrossRef
- Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci USA. 2007;104:270–5. CrossRef
- Takeshita F, Minakuchi Y, Nagahara S, Honma K, Sasaki H, Hirai K, et al. Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proc Natl Acad Sci USA. 2005;102:12177–82. CrossRef
- Shah K. Current advances in molecular imaging of gene and cell therapy for cancer. Cancer Biol Ther. 2005;4:518–23. CrossRef
- Liu J, Wang Y, Qu X, Li X, Ma X, Han R, et al. In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models. Opt Express. 2010;18:13102–13. CrossRef
- Wang G, Cong W, Durairaj K, Qian X, Shen H, Sinn P, et al. In vivo mouse studies with bioluminescence tomography. Opt Express. 2006;14:7801–9. CrossRef
- Brader P, Riedl CC, Woo Y, Ponomarev V, Zanzonico P, Wen B, et al. Imaging of hypoxia-driven gene expression in an orthotopic liver tumor model. Mol Cancer Ther. 2007;6:2900–8. CrossRef
- Sogawa C, Tsuji AB, Sudo H, Sugyo A, Yoshida C, Odaka K, et al. C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model. Nucl Med Biol. 2010;37:179–87. CrossRef
- Oude Munnink TH, Nagengast WB, Brouwers AH, Schröder CP, Hospers GA, Lub-de Hooge MN, et al. Molecular imaging of breast cancer. Breast. 2009;18 Suppl 3:S66–73.
- Smith TA. Towards detecting the HER-2 receptor and metabolic changes induced by HER-2-targeted therapies using medical imaging. Br J Radiol. 2010;83:638–44. CrossRef
- Glunde K, Jacobs MA, Bhujwalla ZM. Choline metabolism in cancer: implications for diagnosis and therapy. Expert Rev Mol Diagn. 2006;6:821–9. CrossRef
- Sega EI, Low PS. Tumor detection using folate receptor-targeted imaging agents. Cancer Metastasis Rev. 2008;27:655–64. CrossRef
- Zhu A, Lee D, Shim H. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol. 2011;38:55–69. CrossRef
- Lindner U, Lawrentschuk N, Trachtenberg J. Image guidance for focal therapy of prostate cancer. World J Urol. 2010;28:727–34. CrossRef
- Bioluminescence Imaging Serves as a Dynamic Marker for Guiding and Assessing Thermal Treatment of Cancer in a Preclinical Model
Annals of Surgical Oncology
Volume 19, Issue 9 , pp 3116-3122
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- 1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- 2. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA