A folate receptor–targeted NIR-II probe improves intraoperative imaging and surgery of metastatic ovarian cancer

Abstract

Intraoperative fluorescence imaging holds great promise for achieving complete cytoreduction in ovarian cancer, but its clinical utility is currently constrained by the limitations of existing imaging agents. In particular, the leading clinical probe, OTL38, operates in the near-infrared I (NIR-I; 700 to 1000 nanometers) window, which suffers from limited tissue penetration and suboptimal resolution. Here, a folate receptor α (FRα)–targeted NIR-II (1000 to 3000 nanometers) imaging probe was developed by incorporating a 4-(4-iodophenyl)butanoic acid moiety. This structural modification enables albumin binding, thereby prolonging systemic circulation and enhancing accumulation in FRα-positive tumors. In murine models of peritoneal metastasis, our probe enabled precise visualization of occult lesions undetectable by the naked eye. Compared to OTL38, this probe demonstrated superior tumor detection sensitivity (90.20% versus 78.75%) and allowed for the reliable identification of elusive lesions less than or equal to 3 millimeters in diameter. These findings highlight the potential of albumin-binding NIR-II imaging strategies to overcome the limitations of current clinical probes and enhance precision fluorescence–guided surgery.