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（由申请人提供）：该生物医学研究补助金的主要目标是将成像剂转化为术中癌症检测和图像引导手术，一半的癌症患者接受手术切除肿瘤，这是患者生存的最重要的预测因素。是原发肿瘤的完整手术切除，引流淋巴液然而，高达 40% 的手术患者在切除后离开手术室时仍残留有恶性细胞，因此，迫切需要开发新的创新技术来帮助外科医生确保完全切除肿瘤。我们提出了一种新技术，可以在标准护理癌症手术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。适用的针对实体瘤，该项目专门致力于改善肺腺癌（最具侵袭性的人类恶性肿瘤之一）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，在叶酸的临床试验方面具有协同专业知识。生物学、化学、肺部病理学、胸外科和兽医学。拟议的工作将优化三种不同类型的造影剂，用于转化术中成像临床试验。第一种造影剂使用叶酸来靶向结合的近红外染料。叶酸-NIR 药物将在针对肺腺癌患者的首次人体临床试验中进行评估，以确定是否有益处。第二种造影剂使用相同的靶向方法将 EGFR 和 CCK2R 的近红外染料传递到癌细胞，从而更好地对埋藏在组织中的病变细胞进行更好的成像。允许精确的肿瘤定位和更准确地切除癌症，而无需侵犯肿瘤包膜或种植体腔。