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: 10061561
• 负责人: John V Frangioni
• 金额: $ 74.68万
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10061561
• 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; Consumption; Contrast Media; Detection; Development; Diagnostic Neoplasm Staging; Dose; Ensure; Europe; Evaluation; Excision; Fluorescence; Freeze Drying; Goals; Grant; Hour; Human; Human Volunteers; Image; Imaging technology; Industrialization; Industry; Infrastructure; Institution; International; Ionizing radiation; Label; Lasers; Left; Letters; Light; Lighting; Location; Lung; Lymph Node Dissections; Lymph Node Mapping; 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 Personnel; Resected; Risk; Sampling; Software Engineering; Staging; Sterility; Structure; Surgeon; System; Technology; Testing; Thoracoscopes; Time; Tissues; Toxicology; Video-Assisted Thoracic Surgery; clinical translation; experience; first-in-human; fly; genotoxicity; imaging Segmentation; imaging platform; imaging system; innovation; intravenous injection; lens; lymph nodes; millimeter; minimally invasive; molecular imaging; new technology; novel; phase 1 testing; 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. 项目概要/摘要 非小细胞肺癌（NSCLC）的分期需要对肺淋巴进行综合评估 淋巴结，通过肺切除期间的完整淋巴结切除术或通过淋巴结取样 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，完全纵隔淋巴结清扫术 (MLND) 和纵隔淋巴结清扫术之间没有区别 更有限的纵隔淋巴结取样 (MLNS)，前提是至少采集 18 个淋巴结 被发现并切除。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 当最新的 ACOSOG 建议包括来自 2R、4R、7、8、9 站的特定淋巴结时 10R 位于右胸部，4L、5、6、7、8、9 和 10L 位于左胸部。目前，淋巴结取样 肺部修复非常耗时且技术上具有挑战性，这反过来又增加了并发症的风险 错过了淋巴结。非小细胞肺癌分期的理想技术将提供灵敏且实时的 通过直径 5 毫米的胸腔镜识别肺淋巴结，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、不可见、近红外 (NIR) 荧光灯来突出显示 手术期间的一个或多个目标。我们的两项最新创新包括微创 FLARE® 系统 与视频辅助胸腔镜手术 (VATS) 和靶向 NIR 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中的每个淋巴结 静脉注射。由于近红外光可穿透活体组织和血液几毫米，因此 技术使 NSCLC 的 MLNS 能够实时且高灵敏度地进行。 我们的长期目标是最大限度地缩短麻醉时间、最大限度地降低并发症发生率并最大化淋巴 NSCLC 患者的淋巴结取样。为了实现这一目标，我们组建了一支国际团队 来自学术界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）。每个机构都拥有经过验证的核心能力和独特的基础设施， 进行合并和利用以完成赠款的目标。具体来说，我们将优化 5 毫米直径 胸腔镜能够同时进行彩色视频、700 nm NIR 荧光和 800 nm 荧光， 开发符合 cGMP 的泛淋巴结药物 CUR-PS327（800 nm 峰值）的合成和无菌灌装 排放），执行临床试验申请（相当于 IND）以实现毒理学，并执行 1A 阶段 （正常人类志愿者）和 1B 期（接受 MLNS 的非小细胞肺癌患者）首次人体临床试验 LUMC 药物研究中心的技术。 完成具体目标将使这项新技术对护理产生重大影响 肺癌患者。

项目成果

Intraoperative Near-Infrared Fluorescence Imaging of Thymus in Preclinical Models.

临床前模型中胸腺的术中近红外荧光成像。

• DOI: 10.1016/j.athoracsur.2016.09.050
• 发表时间: 2017
• 期刊: The Annals of thoracic surgery
• 作者: Wada,Hideyuki;Hyun,Hoon;Kang,Homan;Gravier,Julien;Henary,Maged;Bordo,MarkW;Choi,HakSoo;Frangioni,JohnV
• 通讯作者: Frangioni,JohnV

Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance.

• DOI: 10.1007/s00464-016-5007-6
• 发表时间: 2017-02
• 期刊: SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
• 影响因子: 3.1
• 作者: Boogerd, Leonora S. F.;Handgraaf, Henricus J. M.;Lam, Hwai-Ding;Huurman, Volkert A. L.;Farina-Sarasqueta, Arantza;Frangioni, John V.;van de Velde, Cornelis J. H.;Braat, Andries E.;Vahrmeijer, Alexander L.
• 通讯作者: Vahrmeijer, Alexander L.

Accurate Prediction of Tissue Viability at Postoperative Day 7 Using Only Two Intraoperative Subsecond Near-Infrared Fluorescence Images.

• DOI: 10.1097/prs.0000000000003009
• 发表时间: 2017-02
• 期刊: Plastic and reconstructive surgery
• 影响因子: 3.6
• 作者: Wada H;Vargas CR;Angelo J;Faulkner-Jones B;Paul MA;Ho OA;Lee BT;Frangioni JV
• 通讯作者: Frangioni JV