Fluorescence lifetime-based tumor contrast enhancement using exogenous probes

使用外源探针进行基于荧光寿命的肿瘤对比度增强

• 批准号: 10775262
• 负责人: Anand T.N. Kumar
• 金额: --
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2023-12-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10775262
• 关键词: Aerodigestive Tract; Affect; Algorithms; Beds; Binding; Brain; Cancerous; Cell Culture Techniques; Classification; Clinical; Clinical Research; Custom; Cutaneous; Detection; Development; Diagnostic; Diagnostic Neoplasm Staging; Dyes; Environment; Excision; Exhibits; FDA approved; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Future; Goals; Head and Neck Cancer; Head and Neck Neoplasms; Head and Neck Surgery; Head and neck structure; Histology; Image; Image-Guided Surgery; Imaging Device; Imaging Techniques; Indocyanine Green; Injections; Institutional Review Boards; Label; Light; Liver; Malignant Neoplasms; Maps; Measurement; Methods; Microscopy; Modeling; Mohs Surgery; Molecular Target; Normal tissue morphology; Oncology; Operative Surgical Procedures; Optics; Palpation; Pathology; Patient Schedules; Patients; Penetration; Pre-Clinical Model; Recurrent disease; Sensitivity and Specificity; Solid; Specimen; Standardization; Survival Rate; System; Time; Tissue Stains; Tissues; Translating; Tumor Tissue; Validation; Visual; Visualization; Width; antibody conjugate; attenuation; bone; cancer cell; cancer surgery; cancer type; clinical optical imaging; contrast enhanced; disease diagnosis; dosage; experience; fluorescence imaging; imaging agent; imaging biomarker; imaging modality; imaging platform; imaging system; improved; light intensity; malignant mouth neoplasm; nanosecond; novel; novel strategies; optical imaging; phantom model; portability; pre-clinical; preclinical study; receptor; soft tissue; targeted imaging; tool; tumor; tumor specificity; uptake

Imaging techniques that can enhance tumor contrast against non-specific background can significantly impact diagnostic and surgical applications in oncology. Fluorescence optical imaging is being evaluated for disease diagnosis and surgical treatment, using probes that either preferentially accumulate in tumors, or are antibody conjugated to label tumor-specific receptors. While there has been a significant progress in the development of molecularly targeted near infrared fluorescent probes, background fluorescence from non-specific probe accumulation remains a major confound that reduces sensitivity and specificity for tumor detection. Even when the probe clearance is rapid, tissue autofluorescence can be significant compared to the tumor fluorescence. Existing clinical optical imaging systems primarily employ fluorescence intensity-based imaging. Fluorescence intensity strongly depends on tissue attenuation and experimental factors such as excitation light intensity, and therefore cannot distinguish tumor bound probe from non-specific probe or tissue autofluorescence on an absolute scale. Our preclinical and clinical studies indicate that the fluorescence lifetimes of tumor and normal tissue in subjects injected with cancer targeted probes are distinct and independent of experimental parameters under typical conditions. We have shown that this FLT contrast dramatically improves the accuracy for tumor vs. normal classification compared to intensity-based imaging using the FDA-approved near infrared fluorescent dye, Indocyanine green (ICG). Building on this exciting finding, the goal of this proposal is to robustly validate fluorescence lifetime as a contrast mechanism for tumor identification in oral cancers using ICG. We will develop a portable time domain imaging system for concurrent intraoperative imaging and surgical specimen mapping and optimize the system using preclinical models. Subsequently, we will validate the system for intraoperative imaging and specimen margin assessment using clinical studies in head and neck cancer surgery patients systemically injected with ICG, and determine the dosage and injection time points that provide optimal accuracy for tumor vs normal classification. This proposal will also lead to future applications of lifetime contrast to enhance accuracy of tumor detection in other cancers, using ICG and novel cancer targeted probes currently under development.

可以增强与非特异性背景对比的肿瘤对比的成像技术可以 显着影响肿瘤学中的诊断和手术应用。荧光光学成像是 使用优先的探针评估疾病诊断和手术治疗 积聚在肿瘤中，或者是抗体与标记肿瘤特异性受体的抗体。那里有 在分子靶向近红外荧光的发展方面取得了重大进展 探针，非特异性探针积累的背景荧光仍然是主要的混杂 这降低了肿瘤检测的敏感性和特异性。即使探测清除率很快， 与肿瘤荧光相比，组织自动荧光可能很重要。现有的临床 光学成像系统主要采用基于荧光强度的成像。荧光 强度在很大程度上取决于组织衰减和实验因素，例如激发光 强度，因此无法区分肿瘤结合的探针与非特异性探针或组织 绝对尺度上的自动荧光。我们的临床前和临床研究表明 注射癌症探针的受试者中肿瘤和正常组织的荧光寿命为 在典型条件下独立于实验参数。我们已经表明 这种FLT对比显着提高了肿瘤与正常分类的准确性 使用FDA批准的近红外荧光染料，吲哚氰胺绿色的基于强度的成像 （ICG）。在这一令人兴奋的发现的基础上，该提案的目标是稳健验证荧光 生命周期是使用ICG在口服癌症中肿瘤鉴定的对比机制。我们将发展一个 可同时进行术中成像和手术标本的便携式时域成像系统 使用临床前模型映射和优化系统。随后，我们将验证系统 用于使用头颈临床研究的术中成像和标本边缘评估 癌症手术患者系统地注射了ICG，并确定剂量和注射时间 为肿瘤与正常分类提供最佳精度的点。该建议也将导致 使用寿命对比的未来应用，以增强其他癌症中肿瘤检测的准确性，并使用 ICG和新型癌症针对目前正在开发的探针。