Testing Fluorescently Labeled Probes for Nerve Imaging during Surgery

描述（由申请人提供）：目前手术中神经的识别使用不可量化的标准，如解剖结构，质地，颜色，与周围结构的关系，以区分神经和非神经组织。在创伤、肿瘤侵袭或感染的情况下，使用上述标准进行神经识别可能具有挑战性。我们已经通过噬菌体展示确定了一个肽序列，神经肽41 (NP41)，在全身给药后，与邻近的非神经组织相比，它优先结合周围神经。在啮齿类动物体内系统注射这种肽可在2小时后产生特异性神经标记。有用的神经特异性荧光在单次静脉注射后持续长达8小时，与单独使用白光反射的可视化相比，可以更准确地识别小的和埋藏的神经分支。在这项研究中,我们建议完成以下具体目标:1)证明的概念在使用NP41外科分子指导在动物模型和人类头部和颈部的神经切除,2)证明在使用神经多肽标签的概念自主神经沿前列腺追逐在切除动物模型和人类标本,3)优化NP41准备临床前测试神经有潜力提供特定的荧光标签

DESCRIPTION (provided by applicant): Current identification of nerves during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, 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 may be challenging. We have identified a peptide sequence, Nerve Peptide 41 (NP41) through phage display that preferentially binds to peripheral nerves compared to adjacent non-nerve tissue after systemic administration. Systemic injection of this peptide into rodents results in specific nerve labeling beginning at 2 hours. Useful nerve-specific fluorescence lasts up to 8 hours following a single intravenous injection, allowing more accurate identification of small and buried nerve branches when compared to visualization with white light reflectance alone. In this study, we propose to accomplish the following specific aims: 1) Show proof of concept in using NP41 for surgical molecular guidance in animal models and in excised human nerves of the head and neck, 2) Show proof of concept in using nerve peptides for to label the autonomic nerves coursing along the prostate gland in animal models and in excised human specimens, 3) Optimize NP41 in preparation for preclinical testing A nerve specific fluorescent label has the potential to provide surgeons with a molecular marker visualizable in real time to distinguish nerve from non-nerve tissue, thereby improving surgical accuracy and avoid inadvertent injury. Together, the above studies will yield several proof of concept studies in animal models of head and neck surgery and prostate surgery to test the surgical outcome using fluorescence labeling of nerves with the aim toward eventual use of NP41 during head and neck surgery and nerve-sparing radical prostatectomy in patients. PUBLIC HEALTH RELEVANCE: Current identification of nerves during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, relationship to surrounding structures to distinguish nerves from non-nerve tissues. We have identified a peptide sequence, Nerve Peptide 41 (NP41) through phage display that preferentially binds to peripheral nerves compared to adjacent non-nerve tissue after systemic administration. The aim of this study is to develop several proof of concept studies in animal models of head and neck surgery and prostate surgery to test the surgical outcome using fluorescence labeling of nerves with the aim toward eventual use of NP41 during head and neck surgery and nerve-sparing radical prostatectomy in patients.