Testing Fluorescently Labeled Probes for Nerve Imaging during Surgery

在手术期间测试用于神经成像的荧光标记探针

基本信息

批准号：
8399499
负责人：
Quyen Nguyen
金额：
$ 34.88万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-08 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8399499
关键词：
Anatomy Animal Model Binding Biological Preservation Biotin Color Dendrimers Digestion Dimerization Dyes Evaluation Facial nerve structure Fluorescence Glycoproteins Head and Neck Surgery Head and neck structure Hour Human Image Imagery Infection Injection of therapeutic agent Injury Label Laryngeal Nerves Light Modeling Molecular Molecular Target Nerve Operative Surgical Procedures Outcome Parotid Neoplasms Patients Peptides Peripheral Nerves Phage Display Preclinical Testing Preparation Prostate Prostatectomy Prostatic Neoplasms Proteins Radical Prostatectomy Rodent Rodent Model Singlet Oxygen Specimen Structure Surgeon Testing Texture Thyroidectomy Time Tissues Trauma Tumor Cell Invasion autonomic nerve cyanine dye fluorophore improved intravenous injection molecular marker novel prostate surgery protein aminoacid sequence thyroid neoplasm tumor xenograft

项目摘要

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.

描述（由申请人提供）：目前手术期间神经的识别利用不可量化的标准，例如解剖结构、纹理、颜色、与周围结构的关系来区分神经和非神经组织。在外伤、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。我们通过噬菌体展示鉴定了一种肽序列，即神经肽 41 (NP41)，在全身给药后，与邻近的非神经组织相比，该序列优先与周围神经结合。将这种肽全身注射到啮齿类动物体内，会在 2 小时后开始产生特定的神经标记。单次静脉注射后，有用的神经特异性荧光可持续长达 8 小时，与单独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，我们建议实现以下具体目标：1）展示使用 NP41 在动物模型和切除的人类头颈部神经中进行外科分子指导的概念证明，2）展示使用神经肽的概念证明用于标记动物模型和人体切除标本中沿前列腺流动的自主神经，3) 优化 NP41，为临床前测试做准备神经特异性荧光标记有可能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损伤。总之，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验证研究，以使用神经荧光标记测试手术结果，目的是最终在头颈手术和神经保留过程中使用 NP41患者接受根治性前列腺切除术。公共健康相关性：目前手术期间神经的识别利用解剖学、纹理、颜色、与周围结构的关系等不可量化的标准来区分神经和非神经组织。我们通过噬菌体展示鉴定了一种肽序列，即神经肽 41 (NP41)，在全身给药后，与邻近的非神经组织相比，该序列优先与周围神经结合。本研究的目的是在头颈手术和前列腺手术的动物模型中开展几项概念验证研究，以使用神经荧光标记测试手术结果，旨在最终在头颈手术和神经手术中使用 NP41。避免患者接受根治性前列腺切除术。