MOLECULAR IMAGING CORE

对PDAC的发展、维持和治疗效果的无创、纵向成像是本P01所有部分的基本方面。核心有两个具体用途：a)作为执行和协助所有活体成像实验的高科技核心和智力资源；b)作为创新的研究核心，为来自不同项目的高优先级目标开发新的成像协议和代理。这些项目不仅将使用Core来检测肿瘤的位置和大小，而且重要的是还将监测针对特定途径的药物的反应。例如，K-RAS和PI3K通路的激活启动了葡萄糖吸收和代谢的基因；关闭这些通路的药物通常会在肿瘤缩小之前导致18FDG-PET的急剧变化。同样，Myc调节葡萄糖摄取的基因，因此影响Myc途径的药物也有望对葡萄糖摄取和新陈代谢产生严重影响。核心有效地利用现有的成像资源，但特别侧重于PDAC生物学的独特方面和项目中提出的治疗干预措施。具体地说，该核心将提供：a)用于在GEMS中进行PDAC成像的所有常规成像技术和协议；b)临床可翻译的技术和成像协议，包括MRI和PET-CT；c)高通量光学筛查能力；d)定量图像分析的技术专长；e)图像存档和在整个联合体中分发所需的专业知识；f)与项目目标相关的新型成像探针的设计、合成和验证方面的专业知识；g)包括住房在内的小鼠队列中纵向成像的生理支持和后勤支持。这一核心得到了麻省理工学院系统生物学中心的大量基础设施的支持，其中包括广泛的生物化学工作、计算和定量图像分析，以及一个基于网络的生物信息学平台(MlPortal)，以确保获得成像研究。

Noninvasive, longitudinal imaging of PDAC development, maintenance and therapeutic efficacy is a fundamental aspect for all portions of this P01. The core serves two specific purposes: a) as a high-tech core and intellectual resource to perform and assist with all In vivo Imaging experiments and b) as an Innovative research core to develop new Imaging protocols and agents for high priority targets derived from different projects. The Projects will use the Core not only to detect the location and size of tumors, but importantly also to monitor responses to drugs that target specific pathways. For example, activation of the K-Ras and PI3K pathways turns on genes for glucose uptake and metabolism; drugs that turn off these pathways often cause acute changes in 18FDG-PET, prior to tumor shrinkage. Likewise, Myc regulates genes for glucose uptake so drugs that affect the Myc pathway are also expected to have acute effects on glucose uptake and metabolism. The Core efficiently leverages existing imaging resources but focuses specifically on unique aspects of PDAC biology and therapeutic interventions proposed in the Projects. Specifically the core will provide: a) all routine imaging technologies and protocols for PDAC imaging in GEMS, b) techniques and imaging protocols that are clinically translatable including MRI and PET-CT, c) high throughput optical screening capabilities, d) technical expertise for quantitative image analysis, e) the necessary infrastructure and expertise for image archival and distribution throughout the consortium, f) expertise in the design, synthesis and validation of novel imaging probes relevant to the goals of the projects and g) physiologic support and logistics for longitudinal Imaging in cohorts of mice including housing. The core is supported by a substantial infrastructure in the Center for Systems Biology at MGH, which includes a broad biological chemistry effort, computation and quantitative Image analysis, as well as a web-based bioinformatics platform (MlPortal) to assure access to imaging studies.