Engineered imaging nanoparticle for realtime detection of cancer in the tumor bed

用于实时检测肿瘤床中癌症的工程成像纳米颗粒

• 批准号: 8240393
• 负责人: W David Lee
• 金额: $ 21.28万
• 依托单位: LUMICELL, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-27 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240393
• 关键词: Academic Medical Centers; Address; Adjuvant; Adjuvant Therapy; Adopted; Affect; Amino Acid Sequence; Beds; Blinded; Blood; Cancer Detection; Cancer Patient; Canis familiaris; Cells; Clinical; Collaborations; Computer Simulation; Data; Detection; Development; Drug Formulations; Drug Kinetics; Engineering; Equipment; Excipients; Excision; Failure; Fluorescence; Frozen Sections; General Hospitals; Goals; Hand; Health Care Costs; Histopathology; Hospitals; Hour; Human; Image; Imaging Device; Injectable; Injection of therapeutic agent; Intervention; Investigational Drugs; Label; Left; Legal patent; Licensing; Limb structure; Malignant Neoplasms; Massachusetts; Measurement; Measures; Metabolic Clearance Rate; Methods; Metric System; Microscopic; Molecular; Mus; Operative Surgical Procedures; Orthopedics; Pathology; Patient Care; Patients; Performance; Phase; Predictive Value; Preoperative Procedure; Preparation; Proteins; Protocols documentation; Radiation; Recurrence; Repeat Surgery; Resected; Residual Cancers; Residual state; Risk; Risk Factors; Savings; Sensitivity and Specificity; Serum; Signal Transduction; Simulate; Specimen; Speed; Surgeon; System; Techniques; Technology; Testing; Time; Tissues; Toxicology; Universities; Update; Veterinary Schools; base; breast lumpectomy; cancer cell; cancer imaging; cancer surgery; cancer therapy; design; fluorescence imaging; improved; in vivo; malignant breast neoplasm; mathematical model; medical specialties; molecular imaging; nanoparticle; neoplastic cell; novel; oncology; prevent; response; sarcoma; simulation; soft tissue; tomography; tumor; validation studies

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop an imaging agent and detection system for labeling and real- time detection of residual cancer in the tumor bed during sarcoma resection surgery that will be quickly adopted by surgeons/hospitals because it can eliminate or significantly reduce secondary surgeries and local recurrence. Failure to remove cancer cells during surgery is a leading risk factor for local tumor recurrence and subsequent reoperation. For 35% of sarcoma patients, limb-sparing surgery supported by frozen sections, which only analyze a small fraction of the resected tumor, results in local recurrence in the absence of adjuvant therapy, indicating microscopic residual cancer has been left behind. Furthermore, in other cancer surgeries, as in breast lumpectomies, positive margins and secondary surgeries can occur more than 50% of the time. Technology that can assess whether tumor cells have been adequately removed during surgery can have major impact on cancer therapy worldwide as more than two million people undergo cancer surgery every year. Such technology can reduce rates of local recurrence and eliminate the need for secondary surgeries and adjuvant radiation, reducing associated healthcare costs. Lumicell has developed an injectable imaging agent and hand-held imager that can detect single cells with a wide field of view. Our novel detection technology, developed at MIT and licensed to Lumicell, reliably detects microscopic residual cancer cells in vivo during sarcoma resection surgeries in mice. Based upon mouse and dog tests and using our computer simulation of the imaging agent performance we forecast a peak contrast in humans at 36-48 hours from injection. This timeframe is not ideal with the current preoperative procedures for cancer surgery and we wish to re-engineer the imaging agent to achieve the maximum tumor-to-background signal contrast within 18-24 hours from injection. We propose to re-design our cancer-activatable imaging agent with enhanced pharmacokinetics to rapidly reach the tumor and to increase clearance rates from the blood. To reach the level of signal that we believe can be achieved, we propose on Specific Aim 1 to engineer several designs of imaging agents and to characterize their performance in mice and dogs, and then simulate their performance in humans. On Specific Aim 2 we will select one or two candidate imaging agents with the desired performance between 18-24 hours after injection and conduct validation studies in mice (surgery and pathology). PUBLIC HEALTH RELEVANCE: The proposed project aims to address the unmet clinical need for intraoperative assessment of residual cancer cells in the tumor bed after gross tumor resection in cancer patients. A novel method for fast and thorough examination of the tumor bed in real-time will be developed by engineering an imaging agent suitable to for the typical hospital surgical protocols. This will require the refinement of the Lumicell molecular imaging agent design to achieve peak activation in 18-24 hours (current performance is 36-48 hours) from injection. This technology has the potential to save lives, prevent secondary surgeries, minimize patient discomfort and surgical risks, and provide substantial savings in healthcare costs.

描述（由申请人提供）：本提案的总体目标是开发一种成像剂和检测系统，用于在肉瘤切除手术期间标记和真实的实时检测肿瘤床中的残留癌症，该系统将被外科医生/医院迅速采用，因为它可以消除或显著减少二次手术和局部复发。手术中未能去除癌细胞是局部肿瘤复发和随后再次手术的主要风险因素。对于35%的肉瘤患者，由冷冻切片支持的保肢手术，仅分析切除肿瘤的一小部分，在没有辅助治疗的情况下导致局部复发，表明显微镜下残留的癌症已经留下。此外，在其他癌症手术中，如乳房肿块切除术，阳性切缘和二次手术的发生率可能超过50%。能够评估肿瘤细胞是否在手术中被充分去除的技术可以对全球癌症治疗产生重大影响，因为每年有超过200万人接受癌症手术。这种技术可以降低局部复发率，消除对二次手术和辅助放射的需要，降低相关的医疗费用。Lumicell开发了一种可注射的成像剂和手持式成像仪，可以检测具有宽视野的单细胞。我们的新型检测技术由麻省理工学院开发并授权给Lumicell，可在小鼠肉瘤切除手术期间可靠地检测体内微观残留癌细胞。基于小鼠和狗的测试，并使用我们的成像剂性能的计算机模拟，我们预测在注射后36-48小时在人类中的峰值对比度。这个时间范围对于目前的癌症手术的术前程序来说并不理想，我们希望重新设计成像剂，以在注射后18-24小时内实现最大的肿瘤与背景信号对比度。我们建议重新设计具有增强的药代动力学的癌症激活显像剂，以快速到达肿瘤并增加血液中的清除率。为了达到我们认为可以实现的信号水平，我们建议在特定目标1上设计几种成像剂的设计，并表征它们在小鼠和狗中的性能，然后模拟它们在人类中的性能。在特定目标2中，我们将在注射后18-24小时内选择一种或两种具有所需性能的候选显像剂，并在小鼠中进行验证研究（手术和病理学）。 公共卫生关系：该拟议项目旨在解决癌症患者肉眼肿瘤切除后对肿瘤床中残留癌细胞进行术中评估的未满足的临床需求。通过设计适合典型医院的成像剂，将开发一种快速和全面实时检查肿瘤床的新方法 手术方案这将需要改进Lumicell分子成像剂的设计，以在注射后18-24小时（目前的性能为36-48小时）内达到峰值激活。该技术有可能挽救生命、防止二次手术、最大限度地减少患者不适和手术风险，并大幅节省医疗费用。