Near infrared intraoperative molecular imaging of lung adenocarcinoma

肺腺癌近红外术中分子影像

• 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
• 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

 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转化用于术中癌症检测和图像引导手术的成像剂。一半的癌症患者接受手术切除肿瘤。患者生存的唯一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 淋巴结和转移灶。然而，高达 40% 的手术患者离开手术室时，切除后仍残留有恶性细胞。因此，迫切需要开发新的创新技术，帮助外科医生通过描绘肿瘤边缘、识别微转移和引流淋巴结来确保完全切除肿瘤。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。虽然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，在临床试验、叶酸生物学、化学、肺部病理学、胸外科和兽医学方面拥有协同专业知识。拟议的工作将优化三种不同类型的造影剂，用于平移术中成像临床试验。第一种造影剂使用叶酸将结合的近红外染料特异性地靶向恶性组织。叶酸-NIR 药物将在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 术中成像到标准护理手术方法。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，并可以更好地对埋藏在组织中更深的病变细胞进行成像。这将允许精确的肿瘤定位和更准确的癌症切除，而无需侵犯肿瘤包膜或植入体腔。