Near infrared intraoperative molecular imaging of lung adenocarcinoma

肺腺癌近红外术中分子影像

基本信息

批准号：
9198209
负责人：
PHILIP Stewart LOW
金额：
$ 67.46万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9198209
关键词：
Address Applications Grants Biology Biomedical Research Body cavities Cancer Detection Cancer Patient Canis familiaris Cells Characteristics Chemistry Cholecystokinin B Receptor Clinical Clinical Data Clinical Trials Collaborations Companions Contrast Media Curative Surgery Data Detection Development Disease Dyes EGF gene Ensure Epidermal Growth Factor Receptor Excision Faculty Feasibility Studies Folic Acid Follow-Up Studies Genetic Heterogeneity Goals Grant High Prevalence Human Image Image-Guided Surgery Imagery Industry Joints Laboratories Lesion Lung Adenocarcinoma Lung Neoplasms Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Maps Micrometastasis Modeling Molecular Mus Near-infrared optical imaging Neoplasm Metastasis Nodule Operating Rooms Operative Surgical Procedures Optics Paper Patient Care Patient-Focused Outcomes Patients Peer Review Grants Pennsylvania Phase Phenotype Polyps Preparation Primary Neoplasm Production Publishing Pulmonary Pathology Recurrence Relapse Reproducibility Research Project Grants Resectable Resected Residual Tumors Residual state Solid Neoplasm Staging Surgeon Survival Rate Technology Testing Thoracic Surgical Procedures Time Tissues Toxicology Tracer Translating Translations United States Universities Veterinary Medicine Work base bioimaging biomaterial compatibility body cavity cancer care cancer cell cancer imaging cancer surgery capsule clinical application clinically relevant collaborative environment contrast imaging drug development experience image guided imaging agent improved innovation innovative technologies intraoperative imaging lymph nodes lymphatic drainage molecular imaging neoplastic cell new technology operation particle pre-clinical prevent public health relevance standard of care tumor tumor heterogeneity tumor specificity

项目摘要

DESCRIPTION (provided by applicant): The primary goal of this Biomedical Research Grant is to translate imaging agents for intraoperative cancer detection and image-guided surgery. Half of all cancer patients undergo surgery to remove their tumor. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. However, up to 40% of surgical patients leave the operating room with malignant cells remaining after resection. Thus, there are urgent unmet needs to develop new and innovative technologies that can assist the surgeon in ensuring complete tumor resection by delineating tumor margins, and identifying micrometastases and draining lymph nodes. We propose a new technology to image patients at the conclusion of the standard-of-care cancer operation in order to discover residual local disease before completing the surgery. While the proposed technologies are broadly applicable to solid tumors, this project is specifically committed to improving detection of lung adenocarcinomas, one of the most aggressive human malignancies. To accomplish this goal, we have assembled a collaborative team at University of Pennsylvania and Purdue University with synergistic expertise in clinical trials, folate biology, chemistry, lung pathology, thoracic surgery and veterinary medicine. The proposed work will optimize three distinct types of contrast agents for a translational intraoperative imaging clinical trial. The first contrast agent uses folate to target a conjugated NIR dye specifically to malignant tissue. The folate-NIR agent will be evaluated in a first-in- human clinical trial of lung adenocarcinoma patients in order to determine if there is a benefit of intraoperative imaging to standard-of-care surgical approaches. The second contrast agent uses the same targeting approach to deliver a near-infrared dye for EGFR and CCK2R to cancer cells and allow better imaging of diseased cells more deeply buried in the tissues. This will allow for precise tumor localization and more accurate resection of cancers without violating the tumor capsule or seeding the body cavity.

描述（由适用提供）：这项生物医学研究赠款的主要目标是翻译术中癌症检测和图像引导手术的成像剂。在所有癌症患者中，有一半接受手术以切除其肿瘤。患者生存的最重要的预测指标是对原发性肿瘤的完整手术切除，排出淋巴节点和转移性病变。但是，多达40％的手术患者离开手术室，切除后仍保持恶性细胞。这就是要开发新的创新技术的紧急未满足，可以帮助外科医生通过描述肿瘤边缘来确保完全肿瘤切除，并鉴定微转移和排水淋巴结。我们提出了一项新技术，以在治疗标准癌症运作结束时对患者进行成像，以便在完成手术之前发现残留的局部疾病。尽管所提出的技术广泛适用于实体瘤，但该项目专门致力于改善对人类恶性肿瘤最具侵略性的肺腺癌的检测。为了实现这一目标，我们在宾夕法尼亚大学和普渡大学组建了一个合作团队，并在临床试验，叶酸生物学，化学，肺病理学，胸外科和兽医学方面具有协同的专业知识。拟议的工作将优化三种不同类型的对比剂，用于翻译的术中成像临床试验。第一个对比剂使用叶酸将共轭的NIR染料专门针对恶性组织。将在肺腺癌患者的第一次人类临床试验中评估叶酸-NIR剂术中成像，用于护理标准手术方法。第二个对比剂使用相同的靶向方法将近红外染料用于EGFR和CCK2R向癌细胞提供近红外的染料，并可以更好地对更深入组织的解剖细胞进行更好的成像。这将允许精确的肿瘤定位和更准确的癌症切除，而无需违反肿瘤囊或播种体腔。