Mediastinal Lymph Node Identification in Lung Cancer using NIR Fluorescent VATS

使用近红外荧光 VATS 识别肺癌纵隔淋巴结

• 批准号: 9239732
• 负责人: John V Frangioni
• 金额: $ 76.76万
• 依托单位: CURADEL, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-09 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9239732
• 关键词: Academia; Academic Medical Centers; American College of Surgeons Oncology Group; Anesthesia procedures; Applications Grants; Blood; Caliber; Cancer Patient; Chest; Clinical Research; Clinical Trials; Color; Competence; Complication; Computer software; Contrast Media; Detection; Development; Diagnostic Neoplasm Staging; Dissection; Dose; Ensure; Europe; Evaluation; Excision; Fluorescence; Freeze Drying; Goals; Grant; Hour; Human; Human Volunteers; Image; Imaging technology; Industrialization; Industry; Institution; International; Ionizing radiation; Label; Lasers; Left; Letters; Light; Lighting; Location; Lung; Lymph node excision; Malignant neoplasm of lung; Mediastinal lymph node group; Mediastinoscopy; Mediastinum; Netherlands; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Optics; Patient Care; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Positioning Attribute; Postoperative Period; Powder dose form; Process; Randomized Controlled Trials; Recommendation; Reporting; Research; Research Infrastructure; Research Personnel; Resected; Risk; Sampling; Software Engineering; Staging; Sterility; Structure; Surgeon; System; Technology; Testing; Thoracoscopes; Time; Tissues; Toxicology; Video-Assisted Thoracic Surgery; clinical translation; experience; fly; genotoxicity; imaging Segmentation; imaging platform; imaging system; innovation; intravenous injection; lens; lymph nodes; millimeter; minimally invasive; molecular imaging; new technology; novel; prospective; safety study; software development

7. PROJECT SUMMARY/ABSTRACT The staging of non-small cell lung cancer (NSCLC) requires comprehensive evaluation of lung lymph nodes, either via complete lymphadenectomy during pulmonary resection or via sampling of lymph nodes using mediastinoscopy (preoperatively or intraoperatively). Prospective randomized controlled trial Z0030, reported in 2011, reported no difference between a complete mediastinal lymph node dissection (MLND) and a more limited mediastinal lymph node sampling (MLNS), provided that a minimum of 18 lymph nodes were found and resected. However, finding even 18 lymph nodes in the mediastinum is a daunting task, especially when the latest ACOSOG recommendations include specific lymph nodes from stations 2R, 4R, 7, 8, 9, and 10R in the right chest and stations 4L, 5, 6, 7, 8, 9, and 10L in the left chest. Currently, lymph node sampling of the lung is time-consuming and technically challenging, which in turn increases the risk of complications and missed lymph nodes. The ideal technology for NSCLC staging would provide sensitive and real-time identification of lung lymph nodes via a 5-mm diameter thoracoscope, without the need for ionizing radiation. Curadel has developed such a technology. The FLARE® (FLuorescence-Assisted Resection and Exploration) imaging platform uses low levels of safe, invisible, near-infrared (NIR) fluorescent light to highlight one or more targets during surgery. Our two newest innovations include a minimally-invasive FLARE® system compatible with video-assisted thoracoscopic surgery (VATS) and a targeted NIR fluorescent contrast agent (CUR-PS327) that highlights every lymph node in the mediastinum for several hours after a single low-dose intravenous injection. Because NIR light penetrates several millimeters through living tissue and blood, this technology enables MLNS for NSCLC to be performed in real-time and with high sensitivity. Our long-term goal is to minimize anesthesia time, minimize complication rate, and maximize lymph node sampling for patients with NSCLC. To accomplish this goal, we have assembled an international team of highly experienced investigators from academia (Leiden University Medical Center in The Netherlands; LUMC) and industry (Curadel, LLC). Each institution has proven core competencies and unique infrastructures that will be combined and leveraged to complete the aims of the grant. Specifically, we will optimize a 5-mm diameter thoracoscope capable of simultaneous color video, 700 nm NIR fluorescence, and 800 nm fluorescence, develop cGMP-compliant synthesis and aseptic fill-finish of pan lymph node agent CUR-PS327 (800 nm peak emission), perform Clinical Trial Application (IND equivalent) enabling toxicology, and perform Phase 1A (normal human volunteers) and Phase 1B (NSCLC patients undergoing MLNS) first-in-human clinical trials of the technology at the LUMC Centre for Drug Research. Completion of the Specific Aims will position this new technology to have a major impact on the care of patients with lung cancer.

7。项目摘要/摘要 非小细胞肺癌（NSCLC）的分期需要对肺淋巴进行全面评估 节点，通过肺切除期间完整的淋巴结或通过淋巴结取样 使用纵隔镜检查（术前或术中）。前瞻性随机对照试验Z0030， 2011年报道，报告完整的纵隔淋巴结解剖（MLND）和A之间没有差异 只要至少有18个淋巴结 找到并切除。但是，在纵隔中发现甚至18个淋巴结是一项艰巨的任务，尤其是 当最新的AcoSOG建议包括来自2R，4R，7、8、9和的特定淋巴结时 右胸部和电台4L，5、6、7、8、9和10L的10R左胸部的10R。目前，淋巴结采样 肺部是耗时的，在技术上挑战，进而增加并发症的风险 错过淋巴结。 NSCLC分期的理想技术将提供敏感和实时的 通过直径5毫米的胸腔镜鉴定肺淋巴结，而无需电离辐射。 Curadel开发了这样的技术。 Flare®（荧光辅助切除和 探索）成像平台使用低水平的安全，无形，近红外（NIR）荧光灯来突出显示 手术期间一个或多个目标。我们的两项最新创新包括微不足道的Flare®系统 与视频辅助胸腔镜手术（VAT）和有针对性的NIR荧光对比剂兼容 （CUR-PS327）一次低剂量后，突出了纵隔几个小时的每个淋巴结 静脉注射。因为NIR光穿过活的组织和血液穿透了几毫米，所以 技术使MLN可以实时和高灵敏度进行NSCLC。 我们的长期目标是最大程度地减少麻醉时间，最小化并发症率并最大化淋巴 NSCLC患者的节点采样。为了实现这一目标，我们组建了一个国际团队 来自学术界的经验丰富的研究人员（荷兰莱顿大学医学中心； Lumc） 和行业（Curadel，LLC）。每个机构都具有核心竞争力和独特的基础设施 合并并杠杆以完成赠款的目标。具体而言，我们将优化直径5毫米 能够简单彩色视频，700 nm NIR荧光和800 nm荧光的胸腔镜， 开发PAN淋巴结剂CUR-PS327（800 nm峰）的CGMP合成和无菌填充物 发射），执行临床试验申请（IND等效），使毒理学能够执行1A期。 （正常的人类志愿者）和1B期（NSCLC患者接受MLNS） LUMC药物研究中心的技术。 完成特定目标的完成将使这项新技术对护理产生重大影响 肺癌患者。