Tumor-Responsive Fluorogenic Spray for Image-Guided Cytoreduction of Disseminated Ovarian Tumors

Cytoreductive surgery is a major procedure to treat advanced-stage epithelial ovarian cancer by removing tumors and nearby tissues to which the cancer may have spread. Current intraoperative procedures largely rely on the surgeon's discretion, such as naked-eye gross inspection and palpation, which is highly variable. To enhance the precision of fluorescence-guided surgery (FGS) in detecting small peritoneal tumors, we optimized the formulation of CypH-11, a sprayable near-infrared (NIR) tumor-responsive fluorogenic probe. Here, CypH-11 was formulated with the nonionic ethoxylated solubilizer Kolliphor HS 15 and sprayed directly on the exposed abdomen of ovarian tumor-bearing mice. During cytoreductive surgery aided by CypH-11, combined with or without neoadjuvant therapy, we successfully detected and excised submillimeter tumors (<1 mm in diameter) using an FDA-approved NIR video imaging system. Importantly, the overall specificity, which is represented by the true-positive rate for excised tumors, was over 90%, and the false-negative rate was only 2.6%. This fast-acting, easy-to-apply CypH-11 spray can be a powerful tool for real-time FGS, allowing surgeons to visualize and resect tiny tumors without systemic toxicity, thereby achieving a more complete resection of peritoneally disseminated tumors.