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

基本信息

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
项目类别：
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

项目摘要

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）：每年由于结肠癌而丧生超过50,000人，这是美国第三个致命的癌症。该项目的目的是使用独特的拉曼成像微镜检查来改善早期结肠癌筛查，以检测分子靶向的纳米颗粒。将建造并使用能够进行快速非接触式成像的扫描拉曼内窥镜装置，用于对靶向二氧化硅的基于金的纳米颗粒进行图像。颗粒产生拉曼光散射信号，并将在混合物中局部施用，以使比率成像从该靶向颗粒中减去背景信号。拉曼内窥镜使用激光照明纳米颗粒并检测到无弹性的光。我们将制造圆周扫描的拉曼内窥镜，以白光和具有靶向拉曼活性颗粒的结肠癌生物标志物对结肠解剖结构进行成像。拉曼内窥镜已设计用于临床使用，但将通过自发肿瘤（PIRC大鼠）和原发性人异种移植物进行评估。在常规结肠镜检查中将采购去识别的人类结肠癌组织，并通过手术植入动物。将使用QPCR，Western印迹分析和免疫组织化学评估各种结肠癌生物标志物的过表达。选定靶向肿瘤的配体将用于使我们的拉曼纳米颗粒对比剂的表面功能化。我们将首先在大鼠中，然后在大型动物（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，但由于涉及肿瘤的配体，内窥镜兼容性，毒性降低以及对这种恶性检测的实际需求，我们有动力验证结直肠癌的方法。预计该方法将是低风险，因为拉曼内窥镜以前已在人类中使用，并且基于黄金的纳米颗粒相对惰性，而FDA已经批准了一些构造。利用拉曼光谱法的超敏感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，有可能显着影响癌症患者通过较早的癌症检测。