Development of Fluorescent Probes for Highlighting Nerves During Image Guided Surgeries

摘要 外科手术的基本目标是保留功能并将患者的发病率降至最低。 手术中的意外神经损伤是术后患者发病率的主要原因，原因是 外科医生在手术过程中不能观察到神经。手术中的神经损伤可能导致 到慢性疼痛、麻木、永久性瘫痪、大小便失禁或勃起功能障碍。当前 手术中的神经识别使用不可量化的标准，如解剖学、质地、 颜色，以及与周围结构的关系，以区分神经和非神经组织。在……里面 使用上述标准的创伤、肿瘤侵袭或感染、神经识别的情况可以 要特别具有挑战性。使用白光反射，这是照明的标准模式 在手术室中，小神经之间的视觉差异，如远端神经分支 面神经在涎腺肿瘤或海绵体神经手术中的重要性 在根治性前列腺切除术中很重要，而且邻近组织可能是不可察觉的。有一个 未满足的需要改善术中神经的可视化，以保护神经功能和 最大限度地减少术后患者的发病率。目前还没有临床批准的药物可以 术中增强神经对比。在这项提案中，我们的目标是完成1/2期临床 一种新型多肽染料结合物(ALM-488)作为辅助试剂的安全性和有效性试验 手术中神经的可视化。ALM-488是一种已被证明的多肽染料偶联物 在体内绑定和突出运动神经、感觉神经和自主神经。阿鲁姆预计，临床 ALM-488的翻译可能会改变术中神经的可视化，以防止 手术中的意外伤害，从而改善了患者的预后。

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.