Contrast-Enhanced and Image-Guided Surgery of Lung Cancer

肺癌的造影增强和图像引导手术

• 批准号: 8181665
• 负责人: SHUMING NIE
• 金额: $ 137.1万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8181665
• 关键词: Address; Albumins; Animal Model; Animals; Applications Grants; Biocompatible; Cancer Detection; Cancer Patient; Canis familiaris; Caring; Clinical; Clinical Trials; Collaborations; Color; Companions; Complex; Computer software; Contrast Media; Data; Detection; Development; Devices; Diagnosis; Disease; Drainage procedure; Dyes; Enrollment; Environment; Excision; FDA approved; Faculty; Feasibility Studies; Fluorescence; Goals; Gold; Gold Colloid; Health; Human; Image; Image-Guided Surgery; Indocyanine Green; Injection of therapeutic agent; Institution; Institutional Review Boards; Intraoperative Monitoring; Joints; Lasers; Left; Lesion; Lung; Lung Neoplasms; Lymphatic; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Medical; Medical Oncology; Metastatic Lesion; Micrometastasis; Nanotechnology; Nodule; Non-Small-Cell Lung Carcinoma; Operating Rooms; Operative Surgical Procedures; Outcome; Paper; Pathological Staging; Pathology; Patients; Peer Review Grants; Pennsylvania; Phase; Positioning Attribute; Primary Neoplasm; Publishing; Radiation therapy; Radiology Specialty; Recurrence; Reporter; Research Personnel; Research Project Grants; Resectable; Residual Tumors; Resolution; Signal Transduction; Software Engineering; Solid Neoplasm; Staging; Surface; Surgeon; Survival Rate; System; Technology; Temperature; Thoracic Surgeon; Thoracic Surgical Procedures; Time; Toxicology; Translating; Translational Research; Translations; Universities; Woman; Work; base; cancer imaging; cancer surgery; chemotherapy; clinical application; design; human disease; improved; innovation; innovative technologies; instrumentation; light scattering; lymph nodes; men; nanocrystal; nanoparticle; new technology; outcome forecast; plasmonics; pre-clinical; prevent; single molecule; standard of care; tumor

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.

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粒子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。所提出的技术广泛适用于许多类型的实体瘤，但共同努力将针对肺癌，这是最具侵袭性的人类恶性肿瘤之一，也是男性和女性的全球健康问题。总的来说，手术治愈了大约一半的癌症患者，而化疗和放疗只能治愈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、引流淋巴结和转移性病变的完全手术切除。然而，目前，超过40%的接受手术的患者由于遗漏病变而没有完全切除而离开手术室。因此，有迫切的未满足的需求和重大的机会，开发新的和创新的技术，可以帮助外科医生描绘肿瘤边缘，以确定微转移和引流淋巴结，并确定是否肿瘤已被完全删除。为了实现肺癌的这一目标，我们已经组建了一个由三个学术机构（埃默里大学，格鲁吉亚理工大学和宾夕法尼亚大学）的8名高级教师研究人员组成的协作团队，他们在纳米技术，仪器，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业知识。拟议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式光谱设备和宽视场多通道成像系统，用于首次在人体应用。第一类造影剂基于FDA批准的染料（吲哚菁绿色或ICG）及其白蛋白复合物，将用于器械优化和加速临床可行性研究。第二类造影剂基于聚乙二醇化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，其能够将拉曼散射效率提高14-15个数量级，允许在室温下对单分子和单纳米颗粒进行光谱检测和识别。对于两种类型的造影剂，我们将使用具有自然发生的肺肿瘤（与人类疾病最相关）的大型动物（犬）进行肿瘤边缘勾画以及卫星病变、微转移和转移性淋巴结的图像引导切除。此外，我们将进行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。 公共卫生相关性：该拨款申请开发了用于癌症手术的新的创新技术。主要目的是帮助外科医生描绘肿瘤边缘，识别病变淋巴结和微转移，并确定肿瘤是否已被完全切除。联合使用创新的造影剂和光谱仪器有望对降低肺癌术后局部和区域复发率产生重大影响。