Abstract
During cancer surgery, the identification of normal structures such as nerves is difficult owing to anatomical shifts around the tumor, which increases the risk of nerve injury. Accidental nerve damage can lead to severe complications, including chronic pain, numbness, motor dysfunction, aspiration, and respiratory difficulties. Therefore, precise nerve identification and preservation are critical, even when nerves are located near the tumor. Current nerve-targeted fluorescent contrast agents designed for intravenous administration pose potential risks of systemic side effects. To address this, we developed nerve-specific near-infrared (NIR) fluorophores, including NTFP700, for local application at a wavelength of 700 nm and evaluated its ability to selectively image nerves. Additionally, we explored a dual-channel NIR imaging approach by combining NTFP700 with a tumor-targeted contrast agent (cRGD-ZW800-PEG, 800 nm) to enable clear differentiation of nerves and tumors. NTFP700 effectively highlighted nerve structures with strong fluorescence signals, and its application using a dyed-gauze method allowed for improved visualization, particularly in anatomically altered nerve structures. When combined with cRGD-ZW800-PEG, dual-channel NIR imaging successfully distinguished nerves from tumors with distinct fluorescent signals. These findings demonstrate the potential of NTFP700 as a nerve-targeting fluorophore for local application. The integration of NTFP700 with a tumor-targeting contrast agent, combined with the surgeon-friendly dyed-gauze method, provides a promising strategy for precise nerve and tumor differentiation, potentially reducing the risk of nerve-related complications in oncological procedures.