Multimodality Imaging of GI Cancers for Diagnosis and Directed Therapy

了解和控制从发育不良的胃肠道生长肿瘤的转变，需要协调的评价疾病的分子和解剖标志物，使用特定的生化探针，以识别细胞生理学和细胞表面标志物的变化，并建立技术，可以检测和询问结构和功能。为了改善GI癌症的检测，我们提出使用多模态平台在光学成像和光谱学中进行协作转化研究，用于检测由GI上皮产生的早期肿瘤病变。我们已经建立了一个综合的专业研究资源中心，由来自斯坦福大学、范德比尔特大学、佛罗里达大学和加州大学戴维斯分校的研究人员组成。该计划的总体目标是开发一种基于光学和超声的共识过程和方法，通过在超微结构变化的背景下检查分子标志物来优化疾病早期分子标志物的检测。我们将使用荧光造影剂进行功能分析，并使用光学和超声评估解剖变化。在宽视野荧光内窥镜和超声的辅助下，基于光纤的光学探针将用于分析疾病的分子特征。该计划的工程组件旨在使用已建立的白色光/荧光内窥镜和超声系统以及最先进的小型化传感器进行系统集成，用于针对癌症标志物的分子探针的高分辨率/高灵敏度检测。探针化学是完善的，并基于现有的目标。探针包括选择用于结合发育异常上皮的肽，和针对作为恶性肿瘤细胞内标记物的考克斯-2的化合物。该计划提供了一个基础设施，以支持旨在将开发良好的工具和技术转化为临床的子项目。在每一个次级项目中，现有技术的坚实基础支持改进整合和加强早期发现的创新方法。临床团队由具有转化研究跟踪记录的内窥镜医生组成，这些研究将评估患者的集成工具和试剂。我们拥有一支强大的病理学团队，由具有光学成像和光谱学专业知识的病理学家组成，以促进组织病理学标准的验证。该计划中的主要项目有四个具体目标，每个目标都以多学科和有针对性的方法解决。其中包括：i）验证GI癌症的分子标志物作为成像和治疗的靶标，ii）推进用于GI癌症的成像和治疗的分子探针和集成仪器组合，iii）基于验证的分子标志物优化探针-治疗组合，以及iv）临床评估仪器和探针组合。这些目标得到两个具体任务项目和5个核心项目的支持，并由一个执行委员会监督。

Understanding and controlling the transition from dysplasic growth to neoplasia in the gastrointestinal tract requires coordinated evaluation of the molecular and anatomic markers of disease using both specific biochemical probes to recognize alterations in cellular physiology and cell surface markers, and established technologies that can detect and interrogate both structure and function. To improve detection of Gl cancers we propose to perform collaborative translational research in optical imaging and spectroscopy using multimodal platforms for the detection of early neoplastic lesions arising from the Gl epithelium. We have established an integrated Specialized Research Resource Center comprised of investigators from Stanford University, Vanderbilt University, University of Florida and University of California, Davis. The overarching aim of this program is develop a consensus process and methodology based on optics and ultrasound to optimize detection of early molecular markers of disease by examining molecular markers in the context of ultrastructural changes. We will use fluorescence contrast agents for functional analyses and both optics and ultrasound for assessing anatomic changes. Aided by wide-field fluorescence endoscopy and ultrasound, fiberbased optical probes will be used to analyze the molecular signatures of disease. The engineering components of this program are aimed at systems integration using established white light/fluorescence endoscopy and ultrasound systems and state-of-the-art miniaturized sensors for high resolution/high sensitivity detection of molecular probes directed at markers of cancer. The probe chemistries are well-established and based on existing targets. Probes include peptides, selected for binding to dysplastic epithelium, and compounds directed at COX-2 as an intracellular marker of malignancy. The program provides an infrastructure to support subprojects that are aimed at translating well-developed tools and techniques into the clinic. In each subproject, a strong foundation of established technologies supports innovative approaches to improve integration and enhance early detection. The clinical team consists of endoscopists with a track record of translational research that will evaluate the integrated tools and reagents in patients. We have a strong pathology team comprised of pathologists with expertise in optical imaging and spectroscopy to facilitate validation with histopathological standards. The major project in this program has four specific aims that are each addressed in a multidisciplinary and directed approach. These include: i) validation of molecular markers of Gl cancer as targets for imaging and therapy, ii) advancing molecular probes and integrated instrument combinations for imaging and therapy of Gl cancer, iii) optimization of probe-therapy combinations based on validated molecular markers, and iv) clinically evaluate instrument and probe combinations. These aims are supported by two task specific projects and 5 cores with oversight by an executive committee.