Journal
ACS NANO
Volume 13, Issue 5, Pages 5356-5365Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b09829
Keywords
ovarian cancer; cancer imaging; fluorescence-guided surgery; M13 bacteriophage; microscopic cancer debulking; survival improvement
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Funding
- National Cancer Institute [P30-CA14051]
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center (DF/HCC)
- Milano Bicocca University
- Koch Institute Marlena Felter Bradford Research Travel Fellowship
- Mazumdar-Shaw International Oncology Fellowship
- Koch Institute's Marble Center for cancer Nanomedicine
- Julie Fund
- Gynecologic Cancer Translational Research Fund
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Improved cytoreductive surgery for advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of the disease. Optimal debulking reaching no evidence of macroscopic disease is the primary surgical end point with a demonstrated survival advantage. Targeted molecule-based fluorescence imaging offers complete tumor resection down to the microscopic scale. We used a custom-built reflectance/fluorescence imaging system with an orthotopic OC mouse model to both quantify tumor detectability and evaluate the effect of fluorescence image-guided surgery on postoperative survival. The contrast agent is an intraperitoneal injectable nanomolecular probe, composed of single-walled carbon nanotubes, coupled to an M13 bacteriophage carrying modified peptide binding to the SPARC protein, an extracellular protein overexpressed in OC. The imaging system is capable of detecting a second near-infrared window fluorescence (1000-1700 nm) and can display real-time video imagery to guide intraoperative tumor debulking. We observed high microscopic tumor detection with a pixel-limited resolution of 200 mu m. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence image guided surgical resection compared to standard surgery.
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