Testing Fluorescently Labeled Probes for Nerve Imaging during Surgery

描述(申请人提供)：目前手术中神经的识别利用不可量化的标准，如解剖、质地、颜色、与周围结构的关系来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鉴定可能是具有挑战性的。我们已经通过噬菌体展示鉴定了神经肽41(NP41)，它在全身给药后优先与周围神经结合，而不是邻近的非神经组织。在啮齿类动物体内全身注射这种多肽，会在2小时内开始进行特异性神经标记。有用的神经特异性荧光在一次静脉注射后持续长达8小时，与仅使用白光反射进行可视化相比，可以更准确地识别细小和埋藏的神经分支。在这项研究中，我们建议完成以下特定目标：1)在动物模型和切除的人类头颈部神经中使用NP41进行外科分子指导的概念证明，2)在动物模型和切除的人类标本中使用神经肽标记沿前列腺的自主神经的概念证明，3)优化NP41为临床前测试做准备神经特异性荧光标记具有提供 外科医生使用可实时可视化的分子标记来区分神经和非神经组织，从而提高手术准确性并避免意外伤害。综上所述，上述研究将在头颈手术和前列腺手术的动物模型中产生几项概念性研究，以使用神经荧光标记来测试手术结果，目的是最终在头颈手术和患者的保留神经的前列腺癌根治术中使用NP41。 公共卫生相关性：目前手术中神经的识别利用不可量化的标准，如解剖学、质地、颜色、与周围结构的关系来区分神经和非神经组织。我们已经通过噬菌体展示鉴定了神经肽41(NP41)，它在全身给药后优先与周围神经结合，而不是邻近的非神经组织。本研究的目的是在头颈部手术和前列腺手术的动物模型中开展几项概念验证研究，以测试使用神经荧光标记的手术结果，目的是最终在头颈手术和患者的保留神经的前列腺癌根治术中使用NP41。

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.