Real-Time Single-Walled Carbon Nanotube-Based Fluorescence Imaging Improves Survival after Debulking Surgery in an Ovarian Cancer Model

Abstract

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 a 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 μm. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence imageguided surgical resection compared to standard surgery.

Image‐guided tumor surgery: The emerging role of nanotechnology

“…In addition to simple nanoformulations, there are more complex systems that are utilized for the delivery of NIR‐II contrast agents to solid tumors (Cai et al, ). Two unique examples include an SWNT‐coated M13 bacteriophage (Ceppi et al, ) and red blood cell‐based probe (RBCp; Wang, Fan, et al, ). Another innovative NP delivery strategy is in vivo assembly of up/downconversion NPs (U/DCNPs).…”

Biomarkers in ovarian cancer: To be or not to be

“…Improving the resection rate by removing smaller tumor deposits should result in better patient outcomes and potentially increased cures; therefore, improving cytoreductive surgery is a critical need in the treatment of advanced-stage ovarian cancer. 13 The imaging system is capable of detecting single-walled carbon nanotube fluorescence in the second near-infrared window band. This work has led to the development of a novel molecular imaging agent and device to detect subvisible deposits of ovarian cancer cells.…”

“…This work has led to the development of a novel molecular imaging agent and device to detect subvisible deposits of ovarian cancer cells. 13 This technology is ready to be transitioned to the clinic and may usher in a new age of microdebulking for ovarian cancer. 13 The imaging system is capable of detecting single-walled carbon nanotube fluorescence in the second near-infrared window band.…”

“…12 The contrast agent is an intraperitoneal, injectable nanomolecular probe composed of single-walled carbon nanotubes; it is coupled to an engineered M13 bacteriophage carrying a modified peptide targeting secreted protein, acidic and rich in cysteine (SPARC), an extracellular protein overexpressed in many ovarian cancers. 13 The imaging system is capable of detecting single-walled carbon nanotube fluorescence in the second near-infrared window band. This band has distinct advantages in terms of depth of penetration and time for image capture.…”

“…3). 13 This technology is ready to be transitioned to the clinic and may usher in a new age of microdebulking for ovarian cancer.…”