Novel intra-operative peripheral nerve agent for fluorescence guided imaging

Nerve injuries that significantly affect a patient's quality of life are a common complication of major surgeries. Fluorescence-guided surgery (FGS) has become increasingly popular because it allows physicians to position their instruments precisely during surgeries to spare nerves, for example, in radical prostatectomies. Visualization of nerves during oncological surgeries is an unmet clinical need that is under investigation. Here, we address this unmet need with a contrast agent that is selective for peripheral nerves. Our contrast agent combines an existing near infrared (NIR) dye that fluoresces in the 800 region with a naturally-occurring protein of the human nervous system, nerve growth factor (NGF) - a combination termed Nervelight. Due to the fact that exogenously administered NGF localizes to the distal ends of nerves due to guidance by high affinity receptors, our contrast agent binds specifically to, then is endocytosed, and is transported up the nerve via retrograde axonal transport. In the clinical setting during nerve sparing surgeries, the area in question would be incised, and the surgeon could intra-operatively apply the agent to at-risk nerves before removing the tumor. In preliminary studies, after we directly applied the contrast agent to the nerve of interest, the targeted nerve was clearly labeled by this fluorescent imaging agent. In these experiments, visualization was obtained after 10 minutes. Other studies suggest that nerves may be seen for the duration of at least one hour and likely longer. These results suggest that Nervelight can serve as a fluorescence-guided surgical tool that will improve the visualization of at-risk nerves during radical prostatectomies, and possibly other oncological surgeries.