Raman Molecular Imaging for Early Detection of Colon Cancer

拉曼分子成像用于结肠癌的早期检测

• 批准号: 8819022
• 负责人: CHRISTOPHER H CONTAG
• 金额: $ 52万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8819022
• 关键词: Anatomy; Animal Model; Animals; Area; Artificial nanoparticles; Binding; Biological; Biological Markers; Bladder; Blood Circulation; Cancer Detection; Cancer Model; Cancer Patient; Cancerous; Cell surface; Cells; Cervix Uteri; Characteristics; Clinical; Colon; Colon Carcinoma; Colonoscopy; Colorectal Cancer; Contrast Media; Coupled; Depressed mood; Detection; Devices; Diagnostic; Early Diagnosis; Encapsulated; Endoscopes; Endoscopy; Epithelial; Epithelial Cells; Esophagus; Excision; FDA approved; Family suidae; Fiber; Flavoring; Fluorescence; Gene Expression; Genetic Markers; Goals; Gold; Human; Image; Imaging Device; Imaging technology; Immunohistochemistry; Implant; Incidence; Lasers; Lesion; Ligands; Light; Lung; Malignant Neoplasms; Maps; Metals; Methods; Modality; Modeling; Molecular; Molecular Probes; Noise; Optics; Organ; Patients; Performance; Premalignant; Prevention; Procedures; Proteins; Raman Spectrum Analysis; Rattus; Reporting; Risk; Safety; Scanning; Scheme; Screening for cancer; Screening procedure; Sensitivity and Specificity; Signal Transduction; Silicon Dioxide; Staging; Stomach; Surface; Surface Plasmon Resonance; Survival Rate; System; Techniques; Technology; Time; Tissues; Topical application; Toxic effect; United States; Vagina; Western Blotting; Work; Xenograft Model; Xenograft procedure; base; clinically relevant; colorectal cancer screening; design; empowered; eye aid; imaging agent; imaging system; improved; in vivo; insight; instrument; interest; light scattering; meetings; molecular imaging; mortality; multimodality; nanoparticle; novel diagnostics; optical imaging; overexpression; particle; prevent; public health relevance; ratiometric; screening; targeted imaging; tool; tumor

DESCRIPTION (provided by applicant): Over 50,000 lives are lost annually due to colon cancer, making it the third deadliest cancer in the United States. The aim of this project is to improve early-stage colon cancer screening using a unique Raman imaging microendoscope to detect molecularly targeted nanoparticles. A scanning Raman endoscope device capable of fast non-contact imaging will be built and used to image targeted silica-encapsulated, gold-based nanoparticles. The particles produce a Raman light scattering signal and will be administered topically to the colon in mixtures that enable ratiometric imaging to subtract out background signal from that targeted particles. The Raman endoscope, using laser light, illuminates the nanoparticles and detects the inelastically scattered light. We will fabricate the circumferential-scanning Raman endoscope to image the colon anatomy with white light as well as colon cancer biomarkers with targeted Raman-active particles. The Raman endoscope has been designed for clinical use but will be evaluated with spontaneous tumors (Pirc rats) and primary human xenografts. De-identified human colon cancer tissues will be procured during routine colonoscopy and surgically implanted into animals. Overexpression of various colon cancer biomarkers will be assessed on these human colon cancer tissues using qPCR, western blot analysis and immunohistochemistry. Selected tumor-targeting ligands, will be used to functionalize the surface of our Raman nanoparticle contrast agents. We will assess tumor targeting efficiency and the performance of our Raman endoscope first in rats and then in large animals (porcine). Although this novel diagnostic strategy is not limited to the colon, we are motivated to validate our approach with colorectal cancer due to the availability of tumor-targeting ligands, endoscope compatibility, reduced toxicity and a real need for improved detection of this malignancy. The approach is expected to be low risk because Raman endoscopes have previously been used in humans and because gold based nanoparticles are relatively inert with some constructs already approved by the FDA. Harnessing the ultrasensitive detection and multiplexing capabilities of Raman spectroscopy for the detection of cancer could serve as a powerful diagnostic tool with the potential to significantly impact the survival rate of cancer patients by earlier cancer detection.

描述（由申请人提供）：每年有超过50，000人因结肠癌而丧生，使其成为美国第三大致命癌症。该项目的目的是使用独特的拉曼成像显微内窥镜检测分子靶向纳米颗粒来改善早期结肠癌筛查。一种能够快速非接触成像的扫描拉曼内窥镜设备将被构建并用于对目标二氧化硅封装的基于金的纳米颗粒进行成像。颗粒产生拉曼光散射信号，并将以混合物的形式局部施用到结肠，所述混合物使得比率成像能够从靶向颗粒中减去背景信号。使用激光的拉曼内窥镜照射纳米颗粒并检测非弹性散射光。我们将制作圆周扫描拉曼内窥镜，以利用白色光对结肠解剖结构进行成像，以及利用靶向拉曼活性颗粒对结肠癌生物标志物进行成像。拉曼内窥镜设计用于临床，但将使用自发性肿瘤（Pirc大鼠）和原发性人类异种移植物进行评价。将在常规结肠镜检查期间获取去识别的人结肠癌组织，并通过手术植入动物体内。将使用qPCR、蛋白质印迹分析和免疫组织化学在这些人结肠癌组织上评估各种结肠癌生物标志物的过表达。选定的肿瘤靶向配体，将用于功能化我们的拉曼纳米粒子造影剂的表面。我们将评估肿瘤靶向效率和性能的拉曼内窥镜首先在大鼠，然后在大型动物（猪）。虽然这种新的诊断策略不限于结肠，我们的动机，以验证我们的方法与结直肠癌由于肿瘤靶向配体的可用性，内窥镜兼容性，降低毒性和真实的需要改善这种恶性肿瘤的检测。该方法预期风险较低，因为拉曼内窥镜先前已用于人类，并且因为基于金的纳米颗粒相对惰性，其中一些结构已被FDA批准。利用拉曼光谱的超灵敏检测和多路复用能力来检测癌症可以作为一种强大的诊断工具，有可能显著影响癌症患者的存活率。 早期癌症检测的癌症患者。