Two-Color Near-Infrared Fluorescence Guided Surgery Tools Enabling Simultaneous Cancer Margin and Nerve Visualization during Head and Neck Squamous Cell Carcinoma Resection

双色近红外荧光引导手术工具可在头颈鳞状细胞癌切除过程中同时实现癌症边缘和神经可视化

• 批准号: 10603689
• 负责人: Connor William Barth
• 金额: $ 38.62万
• 依托单位: TRACE BIOSCIENCES INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-23 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603689
• 关键词: Adipose tissue; Anatomy; Biological Sciences; Blood Vessels; Cancer Control; Clinical; Clinical Medicine; Clinical Trials; Collaborations; Color; Complex; Contrast Media; Detection; Development; Dose; Ensure; Epidermal Growth Factor Receptor; Excision; Face; Family suidae; Fascia; Fluorescence; Fluorescent Probes; Frequencies; Goals; Head Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Hour; Image; Image-Guided Surgery; Incidence; Injections; Integrins; Lead; Length; Letters; Life; Light; Malignant Neoplasms; Metalloproteases; Modeling; Muscle; Neck Cancer; Nerve; Normal tissue morphology; Operative Surgical Procedures; Outcome; Palpation; Patients; Peptides; Performance; Persistent pain; Pharmacology; Phase; Plague; Preclinical Testing; Procedures; Quality of life; Rattus; Recurrent Laryngeal Nerve; Reporter; Resolution; Rodent; Signal Transduction; Site; Spinal; Structure; Structure of phrenic nerve; Surgeon; Surgical margins; Survival Rate; System; Technology; Technology Assessment; Time; Tissues; Vagus nerve structure; Vertebral column; Visualization; Work; chromophore; clinical imaging; clinical translation; comorbidity; design; experience; falls; fluorescence imaging; fluorescence-guided surgery; fluorophore; head and neck cancer patient; imaging capabilities; imaging probe; imaging system; improved; innovation; intravenous administration; loss of function; manufacturing test; mouse model; nerve damage; neurotransmission; novel; preclinical development; preservation; small molecule; spared nerve; surgery outcome; targeted imaging; tool; tumor; uptake

PROJECT SUMMARY Head and neck squamous cell carcinoma (HNSCC) is the sixth highest incidence cancer worldwide, with >650,000 cases annually. Surgery is a primary treatment option for HNSCC, during which surgeons face two main goals: 1) complete cancer resection and 2) preservation of normal tissue structures such as muscle, blood vessels, and nerves to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissue and reduce life altering comorbidities. In fact, positive surgical margins are found in 20-30% of patients, and nerve damage represents a major surgical comorbidity, with 5-30% of patients experiencing lasting pain or loss of function. Currently, no technology exists to enhance intraoperative cancer and nerve recognition. Thus, technology to provide direct visualization of cancer margins and nerves simultaneously in real time would greatly improve surgical outcomes and reduce comorbidities for HNSCC patients. Fluorescence Guided Surgery (FGS) has successfully integrated into clinical medicine, providing surgeons real-time visualization of important tissues and complex anatomy. Using compact and high-resolution FGS imaging systems, which operate almost exclusively in the near-infrared (NIR, 700-900 nm), surgeons can image targeted fluorescent probes with high contrast at up to centimeter depths. NIR Nerve-specific and HNSCC-targeted probes under development would together provide an integrated FGS tool for HNSCC resection. Several peptide-based FGS imaging probes have demonstrated efficacy in identifying tumor margins and are currently in phase II and III clinical trials, including those targeting epidermal growth factor receptor (EGFR), matrix metalloprotease (MMP), and integrins. We have developed first-in-class NIR nerve-specific fluorescent small-molecule probes that demonstrate high nerve signal to all background tissues (e.g., muscle, adipose, vasculature, fascia, etc.) following intravenous administration in rodents and swine. Importantly, the tumor-targeting FGS probes utilize fluorescent reporters centered at 800-nm wavelengths, while our nerve-specific probes fluoresce at 700-nm wavelengths, providing spectrally distinct tissue detection and compatibility with existing two-color FGS systems. The combination of these two promising technologies would provide a comprehensive, innovative solution to enhance cancer control and nerve sparing during HNSCC resection. This study’s immediate milestones will include (1) characterization of our lead NIR nerve-specific fluorophore for head and neck procedures, (2) quantification of tumor- and nerve-specific FGS probe co-administration performance including cross-talk, and (3) assessment of this technology using a clinical two-color FGS system. This work will result in the first comprehensive FGS tool for cancer resection and nerve sparing during head and neck procedures. The proposed development will provide important proof-of-concept for further development and partnership. In Phase II, the first two-color tumor and nerve targeted FGS studies will be completed in patients undergoing HNSCC resection.

项目概要 头颈鳞状细胞癌 (HNSCC) 是全球发病率第六高的癌症，其中 每年超过 650,000 例病例，手术是 HNSCC 的主要治疗选择，在此期间外科医生面临两种情况： 主要目标：1）彻底切除癌症；2）保留正常组织结构，如肌肉、血液 不幸的是，这些目标并不具有协同作用。 完整的癌症切除通常受到保护正常组织和减少生活改变的努力的限制 事实上，20-30% 的患者存在手术切缘阳性，神经损伤代表了这种情况。 一种主要的手术合并症，5-30% 的患者会出现持续疼痛或功能丧失，目前还没有。 技术的存在是为了增强术中癌症和神经的识别，因此，技术提供了。 同时实时直接观察癌症边缘和神经将大大改善手术效果 荧光引导手术 (FGS) 已成功改善 HNSCC 患者的治疗效果并减少其并发症。 融入临床医学，为外科医生提供重要组织和复杂组织的实时可视化 使用紧凑且高分辨率的 FGS 成像系统，该系统几乎完全在 近红外（NIR，700-900 nm），外科医生可以在高达 正在开发的 NIR 神经特异性和 HNSCC 靶向探针将一起提供厘米深度。 用于 HNSCC 切除的集成 FGS 工具已被证明是多种基于肽的 FGS 成像探针。 识别肿瘤边缘的功效，目前正在进行 II 期和 III 期临床试验，包括针对 我们开发了表皮生长因子受体（EGFR）、基质金属蛋白酶（MMP）和整合素。 一流的近红外神经特异性荧光小分子探针，向所有人展示高神经信号 静脉内给药后的背景组织（例如肌肉、脂肪、脉管系统、筋膜等） 重要的是，靶向肿瘤的 FGS 探针利用以 800 nm 为中心的荧光分子。 波长，而我们的神经特异性探针在 700 nm 波长处发出荧光，提供光谱上不同的 组织检测以及与现有双色 FGS 系统的兼容性 这两者的组合。 有前景的技术将为加强癌症控制提供全面、创新的解决方案 本研究的近期里程碑将包括 (1) 我们用于头颈手术的主要 NIR 神经特异性荧光团的表征，(2) 定量 肿瘤和神经特异性 FGS 探针联合给药性能，包括串扰，以及 (3) 评估 这项技术使用临床双色 FGS 系统，这项工作将产生第一个全面的 FGS 工具。 拟议的开发将用于头颈部手术期间的癌症切除和神经保护。 为第二阶段的进一步开发和合作提供重要的概念验证，第一个双色肿瘤。 神经靶向 FGS 研究将在接受 HNSCC 切除术的患者中完成。