Multimodality Imaging of GI Cancers for Diagnosis and Directed Therapy

胃肠道癌症的多模态成像用于诊断和定向治疗

• 批准号: 8323002
• 负责人: CHRISTOPHER H CONTAG
• 金额: $ 2.83万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323002
• 关键词: Address; Anatomy; Binding; Biochemical; California; Cell physiology; Cell surface; Chemistry; Clinic; Clinical; Combined Modality Therapy; Consensus; Contrast Media; Detection; Disease; Disease Marker; Early Diagnosis; Endoscopy; Engineering; Epithelium; Evaluation; Florida; Fluorescence; Foundations; Gastrointestinal tract structure; Growth; Image; Lesion; Light; Malignant Neoplasms; Methodology; Molecular; Molecular Probes; Molecular Profiling; Neoplasms; Optics; PTGS2 gene; Pathologist; Pathology; Patients; Peptides; Process; Reagent; Research Infrastructure; Research Personnel; Resolution; Resources; Spectrum Analysis; Structure; System; Systems Integration; Techniques; Technology; Translating; Translational Research; Ultrasonography; Universities; Validation; base; cancer diagnosis; improved; innovation; instrument; miniaturize; molecular marker; multidisciplinary; multimodality; neoplastic; optical imaging; programs; sensor; tool

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.

了解和控制胃肠道中从增生性生长到肿瘤的过渡需要使用特定的生化探针对疾病的分子和解剖学标志物进行协调评估，以识别细胞生理学和细胞表面标记的改变，以及可以检测和估算结构和构造和构造的结构和功能。为了改善GL癌的检测，我们建议使用多模式平台在光学成像和光谱中进行协作转化研究，以检测由GL上皮引起的早期新塑性病变。我们建立了一个集成的专业研究资源中心，该研究中心由斯坦福大学，范德比尔特大学，佛罗里达大学和加利福尼亚大学戴维斯分校组成。该计划的总体目的是基于光学和超声制定共识过程和方法，以在超微结构变化的背景下检查分子标记，以优化对疾病早期分子标记的检测。我们将使用荧光对比剂进行功能分析以及光学和超声检查来评估解剖变化。在宽视野荧光内窥镜和超声检查的帮助下，基于光纤的光学探针将用于分析疾病的分子特征。该程序的工程组件针对系统集成，使用已建立的白光/荧光内窥镜和超声系统以及最先进的微型传感器，用于高分辨率/高灵敏度检测针对癌症标志物的分子探针。探针化学成分是完善的，并基于现有目标。探针包括肽，被选为与发育不良上皮结合的肽，以及针对COX-2的化合物作为恶性肿瘤的细胞内标记。该计划提供了一个基础架构，以支持旨在将良好的工具和技术转化为诊所的副标题。在每个子项目中，既定技术的强大基础都支持创新的方法来改善整合并增强早期检测。临床团队由内窥镜检查员组成，具有转化研究的记录，该研究将评估患者的综合工具和试剂。我们有一个强大的病理团队，由具有光学成像和光谱方面的专业知识的病理学家组成，可促进组织病理学标准的验证。该计划中的主要项目具有四个特定目标，每个目标都以多学科和定向方法来解决。其中包括：i）验证GL癌的分子标志物作为成像和治疗的靶标，ii）推进分子探测器和GL癌症成像和治疗的积分仪器组合，iii）优化基于验证的分子标记的探测治疗组合以及iv）临床评估仪器和探针组合。这些目标得到了两个特定于任务的项目和5个核心的支持，并由执行委员会监督。