SignificanceHead and neck squamous cell carcinoma (HNSCC) has the sixth highest incidence worldwide, with >650,000 cases annually. Surgery is the primary treatment option for HNSCC, during which surgeons balance two main goals: (1) complete cancer resection and (2) preservation of normal tissues to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissues, particularly nerves, and reduce life-altering comorbidities.AimCurrently, no clinically validated technology exists to enhance intraoperative cancer and nerve recognition. Fluorescence-guided surgery (FGS) has successfully integrated into clinical medicine, providing surgeons with real-time visualization of important tissues and complex anatomy, where FGS imaging systems operate almost exclusively in the near-infrared (NIR, 650 to 900 nm). Notably, this spectral range permits the detection of two NIR imaging channels for spectrally distinct detection.ApproachHerein, we evaluated the utility of spectrally distinct NIR nerve- and tumor-specific fluorophores for two-color FGS to guide HNSCC surgery. Using a human HNSCC xenograft murine model, we demonstrated that facial nerves and tumors could be readily differentiated using these nerve- and tumor-specific NIR fluorophores.ResultsThe selected nerve-specific fluorophore showed no significant difference in nerve specificity and off-target tissue fluorescence in the presence of xenograft head and neck tumors. Co-administration of two NIR fluorophores demonstrated successful tissue-specific labeling of nerves and tumors in spectrally distinct NIR imaging channels.ConclusionsWe demonstrate a comprehensive FGS tool for cancer resection and nerve sparing during HNSCC procedures for future clinical translation.
Nerve damage ruins the lives of many patients post surgery, significantly affecting post-surgical quality of life. Intraoperative nerve detection is completed using anatomical knowledge and conventional white light visualization when possible. However, nerves can be difficult or impossible to identify by white light visualization and neuroanatomy is often varied between patients. We have developed nerve specific fluorescence guided surgery (FGS) contrast agents that provide real time direct visualization of nerves intraoperatively. 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. Work is underway to complete the preclinical pharmacology and toxicology testing required for a successful investigational new drug application to the FDA for first-in-human clinical trials and translation to surgical use should be feasible within the next five years.
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