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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要我们的目标是开发肺癌荧光引导成像解决方案。每年都有肺癌是美国（>160,000 人）和世界（140 万人）癌症相关死亡的最大原因死亡人数）。该项目的主要策略是开发、表征和测试四种组合靶向近红外造影剂将用于人体以改善患者的手术患有肺癌。很明显，在癌症手术期间使用荧光靶向剂可以突出显示为临床医生检测癌细胞，因此几个小组正在测试分子探针。我们的研究将特别关注肺癌。肺癌是一种异质性很强的肿瘤，其发病范围广泛。可能导致这种疾病的致病因素。拟议的工作将优化四种不同类型的用于转化术中成像临床试验的组合或混合物中的造影剂。这第一种鸡尾酒制剂由叶酸和与近红外染料缀合的 GCPII 组成。这两个对比药剂功能齐全，正在进行人体试验。然而，他们仍然错过了一个重要的肺癌患者的比例。因此，我们将把精力集中在另外两个代理上：CAIX 和 FAP，在本提案中。该目标的目标是整合已准备好用于临床的 NIR 示踪剂使用。我们将在宠物犬中使用小鼠模型和自发性肺癌模型。这四种药物的整合需要研究敏感性和特异性的变化。它将还需要检查这些代理的时间安排以及这些示踪剂的相互作用。如果这杯鸡尾酒如果成功，将为美国头号癌症杀手提供完整的解决方案。