Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated Illumination.

Abstract

Simple SummaryOvarian cancer has a greater mortality rate than all gynecological malignancies combined. While cytoreductive surgery remains the primary therapeutic approach, its success is limited by the inability to visualize all tumor nodules for resection. We developed light activated nano-sized particles derived from red blood cells as potential imaging probes for near infrared fluorescence imaging of tumors during cytoreductive surgery. We present the first demonstration of the use of these nanoparticles in conjunction a spatially-modulated illumination (SMI) modality to image ovarian intraperitoneal tumors in mice. Our findings indicate that, at 24 h post-administration, these nanoparticles accumulated at higher levels in tumors as compared to organs, and that use of SMI enhances the image contrast.Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0–0.5 mm−1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm−1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.