Abstract Body:

Introduction

Nerve damage impacts ~8%, of all surgical outcomes worldwide, significantly affecting post-surgical quality of life for ~25 million patients by incurring undue pain, loss of function, and high costs to healthcare systems. Conventional intraoperative nerve detection uses anatomical knowledge and white light (WL) visualization. However, nerves can be difficult or impossible to identify by conventional methods. Fluorescence-guided surgery (FGS) offers a potential means for enhanced intraoperative nerve identification and preservation.

Methods

Novel near-infrared (NIR), nerve-specific FGS contrast agents that provide real time direct visualization of buried and invisible nerves intraoperatively in both the 700 nm and 800 nm channels of NIR optical imaging. These nerve-specific fluorophores represent the first of their kind and are capable of translation to clinical studies using existing clinical infrastructure of FGS systems. Additionally, these fluorophores have been characterized to assess their nerve visualization performance in canine prostate models and resected human specimens to support clinical utility for prostatectomy. Further, pharmacology and toxicology testing, facilitating translation of selected lead compounds, have been completed to further improve the clinical translation potential of these fluorophores.

Results

Several lead candidates of these novel FGS contrast agents displayed bright NIR nerve-specific fluorescence contrast. The lead NIR nerve-specific fluorophore, BCP-T108-35, enabled buried nerve visualization in a swine iliac nerve where conventional WL visualization was insufficient for nerve identification during robotic surgery. The lead agents also demonstrated compatibility with the da Vinci Firely system to produce high contrast nerve visualization in cavernous nerves following administration to canine prostate and resected human prostate tissue, validating utility for improved nerve identification during prostatectomy.

Conclusion

FGS has the potential to eliminate intraoperative nerve damage. Work is underway towards an investigational new drug application to the FDA for first-in-human clinical trials with these nerve specific fluorophores. Additionally, this technology has applications to reconstructive surgery, where identification of intact and viable nerve tissue is of utmost importance to obtaining positive outcomes. Upon successful translation, this technology will provide real time enhanced visualization of nerves intraoperatively that would be otherwise unidentifiable, allowing more efficient and effective nerve sparing surgery.

Image/Figure:

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Image/Figure Caption:

First-in-class nerve-specific fluorophores provide high nerve tissue contrast. A. IT01-08 and IT05-75 as well as the first NIR nerve-specific fluorophore, BCP-T108-35, showed high nerve specificity. B. BCP-T108-35 showed nerve specificity in the swine iliac nerve visualized using the da Vinci Firefly (left = color, right = green false colored fluorescence). Yellow arrows = nerve. C. Administration of BCP-T108-35 enabled.

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