Testing Fluorescently Labeled Probes for Nerve Imaging during Surgery

描述（由申请人提供）：目前在手术过程中对神经的识别利用不可量化的标准，例如解剖结构、纹理、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鉴定了一种肽序列，神经肽41（NP 41），其在全身给药后与邻近的非神经组织相比优先结合外周神经。将该肽全身注射到啮齿动物中导致在2小时开始的特异性神经标记。有用的神经特异性荧光在单次静脉内注射后持续长达8小时，当与仅用白色光反射的可视化相比时，允许更准确地识别小的和埋藏的神经分支。在本研究中，我们建议实现以下具体目标：1）显示了在动物模型中和在切除的人头颈神经中使用NP 41进行外科分子引导的概念证明，2）显示了在动物模型中和在切除的人样本中使用神经肽标记沿着前列腺行进的自主神经的概念证明，3）优化NP 41以准备临床前测试神经特异性荧光标记具有提供 外科医生可以使用真实的可视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。总之，上述研究将在头颈部手术和前列腺手术的动物模型中产生几个概念验证研究，以使用神经的荧光标记来测试手术结果，目的是在患者的头颈部手术和保留神经的根治性前列腺切除术期间最终使用NP 41。

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.