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(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性癌症。该项目的目的是改进早期结肠癌筛查，使用独特的拉曼成像显微内窥镜检测分子靶向纳米颗粒。将建立一种能够快速非接触成像的扫描拉曼内窥镜设备，并用于对靶向二氧化硅包裹的金基纳米粒子进行成像。这些颗粒产生拉曼光散射信号，并将以混合物的形式局部注射到结肠，使比率成像能够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。我们将制造周向扫描拉曼内窥镜，用白光成像结肠解剖结构，并用靶向拉曼活性颗粒成像结肠癌生物标记物。拉曼内窥镜已经设计用于临床，但将通过自发性肿瘤(Pirc大鼠)和原发人类异种移植进行评估。未鉴定的人类结肠癌组织将在常规结肠镜检查中获得，并通过外科手术植入动物体内。我们将使用定量聚合酶链式反应、蛋白质印迹分析和免疫组织化学的方法来评估不同的结肠癌生物标记物在这些人结肠癌组织中的过度表达。选定的肿瘤靶向配体将用于我们的拉曼纳米造影剂的表面功能化。我们将首先在大鼠身上评估肿瘤靶向效率和我们的拉曼内窥镜的性能，然后在大型动物(猪)中进行评估。尽管这一新的诊断策略并不局限于结肠，但由于肿瘤靶向配体的可用性、内窥镜的兼容性、毒性的降低以及对这种恶性肿瘤的改进检测的真正需要，我们有动力验证我们的方法对结直肠癌的诊断。这种方法的风险预计很低，因为拉曼内窥镜以前曾用于人类，而且基于金的纳米颗粒相对惰性，一些结构已经得到FDA的批准。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的存活率 癌症患者通过更早的癌症检测。