Development of Fluorescent Probes for Highlighting Nerves During Image Guided Surgeries

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Abstract Fundamental goals of surgery are functional preservation and minimizing patient morbidity. Inadvertent nerve injury during surgery is a major cause of post-surgical patient morbidity due to the inability of surgeons to visualize nerves during surgery. Nerve injury during surgery can lead to chronic pain, numbness, permanent paralysis incontinence or erectile dysfunction. Current nerve identification during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, and relationship to surrounding structures to distinguish nerves from non-nerve tissues. In instances of trauma, tumor invasion or infection, nerve identification using the above criteria can be especially challenging. Using white light reflectance, which is the standard mode of illumination in operating rooms, the visual difference between small nerves, such as distal branches of the facial nerve important during surgery for salivary gland neoplasms, or cavernosal nerves important during radical prostatectomy, and adjacent tissue can be imperceptible. There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following surgery. There are currently no clinically approved agents to enhance nerve contrast during surgery. In this proposal, we aim to complete a Phase 1/2 clinical trial to test the safety and efficacy of a novel peptide dye conjugate (ALM-488) as an agent to aid visualization of nerves during surgery. ALM-488 is a peptide dye conjugate that has been shown to bind and highlight motor, sensory and autonomic nerves in-vivo. Alume anticipates that clinical translation of ALM-488 could be transformative for intraoperative visualization of nerves to prevent inadvertent injury during surgery thereby improving patient outcomes.