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.

可以增强肿瘤对非特异性背景的对比度的成像技术可以 显著影响肿瘤学中的诊断和外科应用。荧光光学成像是 用于疾病诊断和手术治疗的评估，使用探针， 在肿瘤中积累，或者是与标记肿瘤特异性受体缀合的抗体。虽然已经 在分子靶向近红外荧光检测技术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一个主要的混淆因素 这降低了肿瘤检测的灵敏度和特异性。即使当探针间隙迅速时， 组织自体荧光与肿瘤荧光相比是显著的。现有临床 光学成像系统主要采用基于荧光强度的成像。荧光 强度强烈地依赖于组织衰减和实验因素 因此不能区分肿瘤结合探针与非特异性探针或组织 绝对规模的自发荧光。我们的临床前和临床研究表明， 在注射了癌症靶向探针的受试者中肿瘤和正常组织的荧光寿命是 在典型条件下的实验参数的不同和独立。我们已经证明 这种FLT对比显著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菁绿色的基于强度的成像 （ICG）。基于这一令人兴奋的发现，该提案的目标是稳健地验证荧光 使用ICG作为口腔癌中肿瘤识别的对比机制。我们将开发一个 用于同时进行术中成像和手术样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，我们将验证该系统 使用头颈部临床研究进行术中成像和标本边缘评估 肿瘤手术患者全身注射ICG，并确定剂量和注射时间 这些点为肿瘤与正常分类提供最佳准确度。这一提议还将导致 寿命对比的未来应用，以提高其他癌症中肿瘤检测的准确性， ICG和目前正在开发的新型癌症靶向探针。