Multi-Spectral Targeted Imaging for Early Detection of Cancer in Barrett's Esopha

描述（由申请人提供）：本项目的长期目标是建立一个多机构、多学科的转化研究中心，通过Barrett食管转化研究网络（BETRNet）加速靶向成像方法在食管腺癌早期检测和预防中的临床应用。将建立3个相互关联的主要研究项目和共享研究资源（core），以开发先进的内窥镜成像技术，通过观察扩增和过表达基因的分子靶点，作为管理巴雷特食管患者的使能技术。在项目1中，将分析基因组数据，以确定基于基因扩增和/或过表达特性的分子靶标。这些靶标将用于在项目2中选择高度特异性的肽，这些肽将被荧光标记用于成像检测。项目3将开发一种多光谱扫描光纤内窥镜，用于在3个荧光通道中对肽板进行实时可视化。独特的仪器设计可以通过标准医疗内窥镜的工作通道，允许同时进行白光成像。该仪器的未来版本可能有12个或更多通道。将开发图像处理算法，在食管远端全景视图上“红旗”病变区域。这种综合成像策略的目的是帮助医生指导高级别不典型增生和早期腺癌的组织活检。将进行1期研究，为未来的多中心临床验证研究做准备。未来的应用将允许实时空间可视化和监测其他目标，包括与干细胞或癌症风险生物标志物相关的目标。此外，随着时间的推移，可以对Barrett食管患者进行分子靶点成像，以更好地了解该疾病的分子机制。这3个核心将支持主要研究项目、试点项目和跨betrnet项目。行政核心将为拨款和监管管理提供支持，包括预算、财务报告、进度报告、人体受试者协议、新药（IND）申请调查和指导委员会代表。生物信息学核心将为基因组、成像和临床数据的统计评估提供主要项目支持，并为组织标本的数据共享和存档提供BETRNet网络支持。验证和病理核心将为验证肽结合活性提供支持，以扩增和过表达的基因靶点用于高级别不典型增生和早期腺癌。

DESCRIPTION (provided by applicant): The broad, long-term objective of this project is to develop a multi-institutional, multi-disciplinary translational Research Center to accelerate the clinical use of targeted imaging methodologies for the early detection and prevention of esophageal adenocarcinoma through the Barrett's Esophagus Translational Research Network (BETRNet). 3 inter-related Primary Research Projects and Shared Research Resources (Cores) will be established to develop advanced endoscopic imaging as an enabling technology for management of patients with Barrett's esophagus by visualizing molecular targets from amplified and overexpressed genes. In Project 1, genomic data will be analyzed to identify molecular targets based on properties of gene amplification and/or overexpression. These targets will be used to select highly specific peptides in Project 2 that will be fluorescent-labeled for detection on imaging. A multi-spectral scanning fiber endoscope will be developed in Project 3 to perform real time visualization of a panel of peptides in 3 fluorescence channels. The unique instrument design can pass through the working channel of a standard medical endoscope to allow for concurrent white light imaging. Future versions of this instrument may have 12 or more channels. Image processing algorithms will developed to "red-flag" diseased regions on a panoramic view of the distal esophagus. This integrated imaging strategy aims to assist the physician in guiding tissue biopsy of high grade dysplasia and early adenocarcinoma that can not been seen otherwise. Phase 1 studies will be performed to prepare for a future multi-center clinical validation study. Future applications will allow for real time spatial visualization and monitoring of other targets, including those associated with stem cells or with biomarkers of cancer risk. Moreover, imaging of molecular targets can be performed in patients with Barrett's esophagus over time to better understand the molecular mechanisms of this disease. The 3 Cores will support the Primary Research Projects, Pilot Projects, and Cross-BETRNet Projects. The Administrative Core will provide support for grants and regulatory management, including budgets, financial reporting, progress reports, human subjects protocols, investigation of new drug (IND) applications, and Steering Committee representation. The Bioinformatics Core will provide support the Primary Projects for statistical evaluation of genomic, imaging, and clinical data and the BETRNet Network for data sharing and archiving of tissue specimens. The Validation & Pathology Core will provide support for validation of peptide binding activity to amplified and overexpressed gene targets in high-grade dysplasia and early adenocarcinoma.