Contrast-Enhanced and Image-Guided Surgery of Lung Cancer

描述（由申请人提供）：这个变革性和转化性研究项目的主要目标是开发革命性的纳米颗粒造影剂和近红外光谱仪器，用于术中癌症检测和图像引导手术。拟议的技术广泛适用于许多类型的实体瘤，但一致的努力将针对肺癌，最具侵略性的人类恶性肿瘤之一，是一个全球性的健康问题，对男性和女性都是如此。总的来说，手术治愈了大约一半的癌症患者，而化疗和放疗只治愈了5%。几乎所有癌症患者生存的唯一最重要的预测因素是原发肿瘤的完全手术切除，引流淋巴结和转移性病变。然而，目前，超过40%的接受手术的患者由于遗漏病灶而没有完全切除就离开了手术室。因此，开发新的创新技术，帮助外科医生描绘肿瘤边缘，识别微转移和引流淋巴结，并确定肿瘤是否已完全切除，迫切的需求和重大的机会尚未得到满足。为了实现肺癌的这一目标，我们在三个学术机构（埃默里大学、佐治亚理工学院和宾夕法尼亚大学）组建了一个由8名高级教员组成的合作团队，他们在纳米技术、仪器仪表、软件工程、放射学、病理学、肺/胸外科和医学肿瘤学方面具有协同专长。提出的工作将优化两种不同类型的近红外造影剂，并将进一步转化为手持光谱设备和宽视场多通道成像系统，首次用于人体应用。第一种造影剂基于fda批准的染料（吲哚菁绿或ICG）及其白蛋白复合物，并将用于设备优化和加速临床可行性研究。第二种造影剂基于聚乙二醇胶体金和表面增强拉曼散射（SERS），这是一类等离子体纳米晶体，能够将拉曼散射效率提高14-15个数量级，允许在室温下对单个分子和单个纳米颗粒进行光谱检测和识别。对于这两种类型的对比剂，我们将使用自然发生的肺肿瘤（与人类疾病最相关）的大型动物（犬）来划定肿瘤边缘，以及图像引导下切除卫星病变、微转移和转移性淋巴结。此外，我们将进行一项I/II期临床试验，并通过招募约30名非小细胞肺癌（NSCLC）患者来检查标准治疗方法是否有益处。

DESCRIPTION (provided by applicant): The primary goal of this transformative and translational research project is to develop revolutionary nanoparticle contrast agents and spectroscopic instrumentation in the near infrared for intraoperative cancer detection and image-guided surgery. The proposed technologies are broadly applicable to many types of solid tumors, but concerted efforts will be directed toward lung cancer, one of the most aggressive human malignancies and a worldwide health problem for both men and women. The overall rationale is that surgery cures approximately half of all cancer patients, while chemotherapy and radiation therapy cure only 5%. The single most important predictor of patient survival for almost all cancers is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. At the present, however, over 40% of patients that undergo surgery leave the operating room without a complete resection due to missed lesions. Thus there are urgent unmet needs and major opportunities to develop new and innovative technologies that can help the surgeon to delineate tumor margins, to identify micrometastases and draining lymph nodes, and to determine if the tumor has been completely removed. To accomplish this goal for lung cancer, we have assembled a collaborative team of 8 senior faculty investigators at three academic institutions (Emory University, Georgia Tech, and the University of Pennsylvania) with synergistic expertise in nanotechnology, instrumentation, software engineering, radiology, pathology, lung/thoracic surgery, and medical oncology. The proposed work will optimize two distinct types of near-infrared contrast agents and will further translate a handheld spectroscopic device and a wide-field multichannel imaging system for first-in-human applications. The first type of contrast agents is based on an FDA-approved dye (indocyanine green or ICG) and its albumin complexes, and will be used for device optimization and accelerated clinical feasibility studies. The second type of contrast agents is based on pegylated colloidal gold and surface-enhanced Raman scattering (SERS), a class of plasmonic nanocrystals that are able to enhance the Raman scattering efficiencies by 14-15 orders of magnitude, allowing spectroscopic detection and identification of single molecules and single nanoparticles at room temperature. For both types of contrast agents, we will use large animals (canines) with naturally occurring lung tumors (most relevant to the human disease) for tumor margin delineation as well as for image- guided resection of satellite lesions, micrometastases, and metastatic lymph nodes. In addition, we will conduct a Phase I/II clinical trial and examine if there is a benefit to standard-of-care approaches by enrolling approximately 30 human patients with non-small cell lung carcinoma (NSCLC). PUBLIC HEALTH RELEVANCE: This grant application develops new and innovative technologies for applications in cancer surgery. The main goal is to help the surgeon to delineate tumor margins, to identify diseased lymph nodes and micrometastases, and to determine if the tumor has been completely removed. The combined use of innovative contrast agents and spectroscopic instrumentation is expected to make a major impact in reducing the local and regional recurrence rates of lung cancer after surgery.