STTR Phase I: Near Infrared Nerve-Specific Fluorophores for Fluorescence-Guided Surgery

STTR 第一阶段：用于荧光引导手术的近红外神经特异性荧光团

• 批准号: 2036434
• 负责人: Connor Barth
• 金额: $ 24.43万
• 依托单位: INHERENT TARGETING, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036434&HistoricalAwards=false
• 关键词: STTR; Phase; Near; Infrared; Nerve

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is the development of a technology that will reduce intraoperative nerve damage using fluorescence imaging to enable surgeons to see the unseen. Intraoperative nerve injury is a major complication of surgery, affecting all specialties and often causing irreparable damage. Nerve damage occurs in ~17% of all surgeries and intraoperative nerve injuries affect 50 million patients annually worldwide, incurring undue pain, loss of function, and high costs to the healthcare system. Currently, no clinically approved technology exists to enhance intraoperative nerve recognition - surgeons rely solely on anatomical knowledge and visualization. The proposed project will finalize development of first-in-kind nerve targeted substance allowing surgeons to “cut by color” – identifying and sparing nerves more effectively to reduce these complications and the associated costs, estimated at $12.5 billion annually.The proposed project is focused on the development of near-infrared nerve-specific fluorophores for fluorescence-guided surgery (FGS) that are clinically viable for translation to human studies. Recent work has allowed modification of the base structures of the fluorophores to significantly improve brightness, solubility, and toxicity while maintaining high nerve specificity. The immediate milestones of the work proposed herein include (1) characterization of a library of benzo[c]phenoxazine small molecule derivatives with chemically tuned water solubility and quantified nerve specificity, (2) elucidation of the biological target and mechanistic understanding of nerve-specificity for the fluorophores, (3) preliminary single-dose toxicology analysis in rodents, (4) quantified pharmacokinetics, pharmacodynamics, and biodistribution to determine the optimal imaging dose and time window, and (5) identification of a lead compound for clinical translation. Successful completion of the proposed work will enable selection of a lead candidate with a proven safety profile and bright, long-lasting (~1 hour) nerve-specific fluorescence for identification of buried nerve structures at up to 1 cm depths.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）I期项目的更广泛影响是开发一种技术，该技术将使用荧光成像减少术中神经损害，以使外科医生能够看到看不见的。术中神经损伤是手术的主要并发症，影响了所有特殊性，并且经常造成无法弥补的损害。在所有手术中，约有17％发生神经损伤，术中神经损伤每年在全球范围内影响5,000万患者，导致une疼痛，功能丧失以及医疗保健系统的高成本。目前，尚无临床认可的技术来增强术中神经识别 - 外科医生仅依赖解剖学知识和可视化。 The proposed project will finalize development of first-in-kind nerve targeted substance allowing surgeons to “cut by color” – identifying and sparing nerves more effectively to reduce these complications and the associated costs, estimated at $12.5 billion One way.The proposed project is focused on the development of near-infrared nervous-specific fluorophores for fluorescence-guided surgery (FGS) that are clinically viable for translation to human studies.最近的工作允许修改荧光团的基础结构，以显着提高亮度，可溶性和毒性，同时保持高神经特异性。本文提出的工作的直接里程碑包括（1）表征苯甲酸苯并噻嗪的库库，具有化学调谐水溶性和量化神经特异性的小分子衍生物，（2）对生物学靶标的和机械理解的神经特异性对氟植物的神经特异性的理解，（3）原始分析毒理学，（3）原始分析毒理学，（3）原始分析毒理学，（3）剂量分析（3）剂量毒性（4）药效学和生物分布以确定最佳成像剂量和时间窗口，以及（5）识别用于临床翻译的铅化合物。成功完成拟议的工作将有助于选择具有可靠的安全性和明亮，持久（约1小时）神经特异性荧光的铅候选人，以识别最高1 cm深度的建筑神经结构。这奖反映了NSF的法规任务，并认为通过基金会的知识优点和广泛的critia criter scritia crietia crietia crietia criter criter criter criter criter critia criter criter criter criter critia criter criter critia criter critia criter critia crietia crietia crietia crietia criter critie criperia均可表现出色。