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.
The core will provide stability to the overall program and allow the investigators to focus on and efficiently address critical issues relevant to the goals of this P01. Centralization of the imaging efforts will also reduce overall mouse costs (by decreasing the number of mice needed in therapeutic studies), provide a higher level of expertise and promote interactions among the participating groups. Added benefits of this core are the high level of quality control, consistency of imaging protocols and reagents and efficient cross-reference of imaging results from different projects.
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