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

描述(由申请人提供)：该项目的广泛、长期目标是开发一个多机构、多学科的转化研究中心，通过巴雷特的食道转化研究网络(BETRNet)加速靶向成像方法的临床应用，以早期发现和预防食管腺癌。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，通过可视化扩增和过度表达的基因的分子靶标，使巴雷特食道患者的治疗成为可能。在项目1中，将分析基因组数据，以根据基因扩增和/或过度表达的特性确定分子靶标。这些靶标将被用来在项目2中选择高度特异的多肽，这些多肽将被荧光标记以用于成像检测。在项目3中，将开发一种多光谱扫描光纤内窥镜，以实时显示3个荧光通道中的一组多肽。独特的仪器设计可以穿过标准医用内窥镜的工作通道，允许同时进行白光成像。此仪器的未来版本可能有12个或更多通道。图像处理算法将被开发成在远端食道的全景图上对病变区域进行“红旗”标记。这一综合成像策略旨在帮助医生指导以其他方式看不到的高度不典型增生和早期腺癌的组织活检。将进行第一阶段研究，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，包括那些与干细胞或癌症风险生物标记物相关的目标。此外，随着时间的推移，可以对Barrett‘s食道患者进行分子靶点成像，以更好地了解这种疾病的分子机制。这3个核心将支持初级研究项目、试点项目和跨BETRNet项目。行政核心将为赠款和监管管理提供支助，包括预算、财务报告、进度报告、人体试验方案、新药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的主要项目以及组织样本的数据共享和存档的BETRNet网络提供支持。验证和病理核心将为验证高级别异型增生和早期腺癌中扩增和过度表达的基因靶标的多肽结合活性提供支持。

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.