Project 2: Near-Infrared Targeted Tracers for Intraoperative Identification of NSCLC

项目2：用于术中识别NSCLC的近红外靶向示踪剂

• 批准号: 10333065
• 负责人: PHILIP Stewart LOW
• 金额: $ 45.74万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-16 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10333065
• 关键词: Address; Adenocarcinoma; Animal Hospitals; Animal Model; Antigens; Applications Grants; Biopsy; Bronchoscopy; Cancer Etiology; Cancer Model; Cancer Patient; Cancerous; Canis familiaris; Cessation of life; Clinic; Clinical; Clinical Trials; Colon Carcinoma; Contrast Media; Data; Detection; Development; Disease; Dose; Drug Kinetics; Dyes; Ensure; FOLH1 gene; FOLR1 gene; Fibroblasts; Fluorescence; Fluorochrome; Folic Acid; Formulation; Genetic Heterogeneity; Goals; Grant; Human; Image; Image-Guided Surgery; In Vitro; Intervention; Libraries; Logistics; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Membrane; Molecular; Molecular Probes; Mus; Nodule; Noise; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Optics; Pathologic; Patient Agents; Patients; Persons; Phenotype; Population; Procedures; Reproducibility; Research; Second Primary Cancers; Sensitivity and Specificity; Testing; Time; Tissues; Tracer; Translations; United States; Work; Xenograft procedure; biomaterial compatibility; cancer cell; cancer imaging; cancer surgery; cancer type; carbonate dehydratase; chemical synthesis; clinical application; efficacy testing; environmental tobacco smoke exposure; experience; experimental study; fibroblast-activating factor; folate-binding protein; human model; image guided; improved; innovation; lung cancer cell; lung imaging; lymph nodes; malignant breast neoplasm; meetings; molecular imaging; mouse model; near infrared dye; phase 2 study; pre-clinical; programs; receptor; success; targeted agent; tumor; tumor microenvironment

Project Summary Our goal is to develop a fluorescence guided imaging solution to lung cancer. Each year, lung cancer is the biggest cause of cancer related deaths in the US (>160,000 people) and the world (1.4 million fatalities). The primary strategy in this Project is to develop, characterize and test a combination of four targeted near-infrared contrast agents that will be used in humans to improve procedures for patients with lung cancer. It is clear that using fluorescent targeted agents during cancer surgery can highlight cancer cells for clinicians, thus several groups are testing molecular probes. Our research will specifically focus on lung cancer. Lung cancer is a very heterogeneous tumor due to the wide range of offending agents that can cause this disease. The proposed work will optimize four distinct types of contrast agents in a combination or cocktail for a translational intraoperative imaging clinical trials. The first cocktail agents are composed of folate and GCPII conjugated to a NIR dye. These two contrast agents are fully functional and are in human trial. However, together, they still miss a significant proportion of patients with lung cancer. Thus, we will be focusing our efforts on two more agents, CAIX and FAP, in this proposal. The goal of this Aim is to integrate the NIR tracers that are ready for clinical use. We will be utilizing both murine models and spontaneous lung cancer models in pet canines. Integration of these four agents will require studying the changes in sensitivity and specificity. It will also require examining the timing of these agents and the interactions of these tracers. If this cocktail is successful, it will provide a complete solution for the number one cancer killer in the United States.

项目摘要 我们的目标是为肺癌开发荧光引导的成像解决方案。每年，肺癌 是美国（> 160,000人）和世界（140万人）与癌症相关死亡的最大原因 死亡）。该项目的主要策略是开发，表征和测试四个 有针对性的近红外对比剂将用于人类改善患者的程序 患有肺癌。显然，在癌症手术期间使用荧光靶向药物可以突出显示 临床医生的癌细胞，因此几个组正在测试分子探针。我们的研究会 特别关注肺癌。由于范围很广，肺癌是一种非常异质的肿瘤 可能导致这种疾病的冒犯药物。拟议的工作将优化四种不同类型的 术中术中成像临床试验中的组合或鸡尾酒中的对比剂。这 首先鸡尾酒剂由叶酸和GCPII组成，并缀合了NIR染料。这两个对比 代理人功能齐全，正在进行人类试验。但是，他们仍然错过了一个重要的 肺癌患者比例。因此，我们将把精力集中在另外两个代理商上，Caix 和FAP，在此提案中。此目的的目的是整合准备临床的NIR示踪剂 使用。我们将在宠物犬中利用鼠模型和自发的肺癌模型。 这四个代理的整合将需要研究灵敏度和特异性的变化。会 还需要检查这些试剂的时间和这些示踪剂的相互作用。如果这个鸡尾酒 成功，它将为美国排名第一的癌症杀手提供完整的解决方案。