Nerve Visualization using Phenoxazine‐Based Near‐Infrared Fluorophores to Guide Prostatectomy

Fluorescence‐guided surgery (FGS) is poised to revolutionize surgical medicine through near‐infrared (NIR) fluorophores for tissue‐ and disease‐specific contrast. Clinical open and laparoscopic FGS vision systems operate nearly exclusively at NIR wavelengths. However, tissue‐specific NIR contrast agents compatible with clinically available imaging systems are lacking, leaving nerve tissue identification during prostatectomy a persistent challenge. Here, it is shown that combining drug‐like molecular design concepts and fluorophore chemistry enabled the production of a library of NIR phenoxazine‐based fluorophores for intraoperative nerve‐specific imaging. The lead candidate readily delineated prostatic nerves in the canine and iliac plexus in the swine using the clinical da Vinci Surgical System that has been popularized for minimally invasive prostatectomy procedures. These results demonstrate the feasibility of molecular engineering of NIR nerve‐binding fluorophores for ready integration into the existing surgical workflow, paving the path for clinical translation to reduce morbidity from nerve injury for prostate cancer patients. Identifying nerves during prostatectomy poses a significant challenge due to their small size, translucency, and narrowness of the pelvis. To address this issue, a library of nerve‐specific fluorophores based on a phenoxazine scaffold has been developed. Formulated derivatives have been shown to be compatible with the robotic‐assisted da Vinci system, allowing for high‐fidelity imaging of prostatic nerves during fluorescence‐guided surgery.