“Imaging Tumor Response to Anticancer Therapies” (Gillies)
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Abstract: The focus of our laboratory is to increase the use of non-invasive functional and molecular imaging to improve cancer diagnosis, care and response to therapy.  An important aspect of this is to use imaging to monitor and predict response to anti-cancer therapies.  There are a large number of imaging biomarkers, a large number of therapies and a large number of cancers.  Each drug-cancer combination may be unique, making it difficult to rationally choose the optimal imaging biomarker.  We believe that imaging in appropriate animal models can be used to narrow down the possibilities and identify biomarkers that may be most efficacious in the clinic.  To this end, we have developed a protocol to image therapy response using a battery of MR-techniques, which allows multiple biomarkers to be directly and empirically compared.  A number of examples will be discussed, including anti-HIF inhibitors.  During the course of this work, an apparent disconnect was observed between VEGF levels and vessel permeability, which had heretofore assumed to be synonymous.  This has led us to investigate the effect of these drugs on vessel permeability more quantitatively with higher resolution, using window chambers.

“DCE-MRI & Fluorescence Microscopy of Microvascular Permeability” (Jennings)
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Abstract: Dynamic contrast enhanced-MRI (DCE-MRI) is a non-invasive, functional method that has been used extensively to measure active changes in microvascular hemodynamics in tumors. Because anti-angiogenic therapies are designed to affect the abnormal blood vessels recruited by tumors, changes in blood volume, blood flow, or other hemodynamic parameters are promising biomarkers that allow for an in vivo assessment of the biological activity of these angiogenic modulators. The ability of DCE-MRI to quantitatively measure response is fundamentally limited by a lack of precise knowledge regarding the relationship between the contrast agent concentration and signal intensity. DCE-MRI does not measure the tracer directly but, rather the effect of tracers on water relaxation. Since water is not exclusively extracellular, exact concentrations must often be inferred. We propose a method by which microvascular hemodynamics as measured by DCE-MRI can be directly compared to the same parameters measured by intravital fluorescence microscopy in a window chamber model. This talk will describe the feasibility of this dual imaging capability to produce meaningfuldata from both fluorescence and MRI which can be quantitatively compared.