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: 9678998
• 负责人: CHRISTOPHER H CONTAG
• 金额: $ 55.83万
• 依托单位: MICHIGAN STATE 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/9678998
• 关键词: Anatomy; Animal Model; Animals; Area; Artificial nanoparticles; Binding; Biological; Biological Markers; Bladder; Blood Circulation; Cancer Detection; Cancer Model; Cancer Patient; Cancerous; Carcinoma; 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 Cells; Esophagus; Excision; Eye; FDA approved; Family suidae; Fiber; Fluorescence; Gene Abnormality; Gene Expression; Genetic Markers; Goals; Gold; Human; Image; Image-Guided Surgery; Imaging Device; Imaging technology; Immunohistochemistry; Implant; Incidence; Lasers; Lesion; Ligands; Light; Lung; Malignant Neoplasms; Maps; Metals; Methods; Modality; Modeling; Molecular; Molecular Probes; Molecular Target; Multimodal Imaging; Noise; Operative Surgical Procedures; Optics; Organ; Patients; Performance; Photobleaching; 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; Stomach; Surface; Surface Plasmon Resonance; Survival Rate; System; Techniques; Technology; Time; Tissues; Topical application; Toxic effect; United States; Vagina; Western Blotting; Xenograft Model; Xenograft procedure; base; cancer biomarkers; clinically relevant; clinically translatable; colon cancer screening; colorectal cancer screening; design; human imaging; imaging agent; imaging study; imaging system; improved; in vivo; insight; instrument; interest; light scattering; metallicity; microendoscope; molecular imaging; mortality; nanoparticle; novel diagnostics; optical imaging; overexpression; particle; prevent; public health relevance; ratiometric; specific biomarkers; targeted biomarker; 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 人死于结肠癌，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来检测分子靶向纳米颗粒，以改善早期结肠癌筛查。将建造一种能够快速非接触式成像的扫描拉曼内窥镜设备，并用于对目标二氧化硅封装的金基纳米颗粒进行成像。这些颗粒产生拉曼光散射信号，并将以混合物形式局部施用于结肠，从而能够进行比例成像以从目标颗粒中减去背景信号。拉曼内窥镜使用激光照射纳米颗粒并检测非弹性散射光。我们将制造圆周扫描拉曼内窥镜，用白光对结肠解剖结构进行成像，并用靶向拉曼活性粒子对结肠癌生物标志物进行成像。拉曼内窥镜专为临床使用而设计，但将用自发肿瘤（Pirc 大鼠）和原代人类异种移植物进行评估。将在常规结肠镜检查期间获取未识别的人类结肠癌组织，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来评估这些人类结肠癌组织中各种结肠癌生物标志物的过度表达。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。我们将首先在大鼠和大型动物（猪）中评估拉曼内窥镜的肿瘤靶向效率和性能。尽管这种新颖的诊断策略不仅限于结肠，但由于肿瘤靶向配体的可用性、内窥镜兼容性、毒性降低以及改进这种恶性肿瘤检测的真正需要，我们有动力验证我们的结直肠癌方法。该方法预计风险较低，因为拉曼内窥镜之前已用于人体，而且金基纳米颗粒相对惰性，某些结构已获得 FDA 批准。利用拉曼光谱的超灵敏检测和多重功能来检测癌症可以作为一种强大的诊断工具，有可能显着影响癌症患者的生存率 癌症患者通过早期癌症检测。