Mediastinal Lymph Node Identification in Lung Cancer using NIR Fluorescent VATS

7.项目摘要/摘要 非小细胞肺癌(NSCLC)的分期需要肺淋巴的综合评估 在肺切除过程中通过彻底的淋巴清扫或通过对淋巴进行采样 使用纵隔镜检查(术前或术中)。前瞻随机对照试验Z0030， 2011年报道，报告称完全纵隔淋巴清扫术(MLND)和 更有限的纵隔淋巴结采样(MLNS)，前提是至少有18个淋巴结 找到并切除了。然而，即使在纵隔中找到18个淋巴结也是一项艰巨的任务，尤其是 当ACOSOG的最新建议包括来自站2R、4R、7、8、9和 右胸为10R，左胸为4L、5、6、7、8、9和10L。目前，淋巴样本的 肺部既耗时又具有技术挑战性，这反过来又增加了并发症和 遗漏了淋巴结。NSCLC分期的理想技术将提供灵敏和实时的 通过直径5毫米的胸腔镜识别肺淋巴结，而不需要电离辐射。 库拉德尔已经开发出了这样一项技术。FLARE®(荧光辅助切除和 探索)成像平台使用低强度的安全、不可见、近红外(NIR)荧光灯来突出显示 手术中的一个或多个靶点。我们的两项最新创新包括微创FLARE®系统 与电视胸镜手术(VATS)和靶向近红外荧光造影剂兼容 (CUR-PS327)，在单次低剂量后数小时内突出显示纵隔内的每个淋巴结 静脉注射。由于近红外光可以穿透几毫米的活组织和血液，这 这项技术使非小细胞肺癌的MLNS能够实时和高灵敏度地进行。 我们的长期目标是最大限度地减少麻醉时间，减少并发症发生率，最大限度地增加淋巴。 非小细胞肺癌患者的结节取样。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) 和工业(Curadel，LLC)。每一家机构都拥有经过验证的核心能力和独特的基础设施，将 合并和利用，以完成赠款的目标。具体地说，我们将优化5毫米直径 可同时拍摄彩色视频、700 nm近红外荧光和800 nm荧光的胸镜， 符合cGMP的PAN淋巴结剂CUR-PS327(800 nm峰)的合成及无菌填充剂的研制 排放)，执行启用毒理学的临床试验应用(相当于IND)，并执行阶段1A (正常人志愿者)和1B期(接受MLNS的非小细胞肺癌患者)首次人体临床试验 LUMC药物研究中心的这项技术。 具体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。

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.