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Abstract #3132

Comparisons of the Efficacy of the Jak1/2 Inhibitor AZD1480 with the VEGF Signaling Inhibitor Cediranib (AZD2171) & Sham Treatments in Mouse Tumors using DCE-MRI, DW-MRI, & Histology

Mary E. Loveless1,2, Deborah Lawson3, Michael Collins3, Deborah Morosini3, Corinne Reimer3, Dennis Huszar3, Jane Halliday4, John C. Waterton4, John C. Gore2,5, Thomas E. Yankeelov2,5

1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States; 2Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States; 3Cancer Bioscience, AstraZeneca, Boston, MA, United States; 4Translational Sciences: Imaging, AstraZeneca, Macclesfield, Cheshire, United Kingdom; 5Radiology & Radiological Science, Vanderbilt University, Nashville, TN, United States

AZD1480 is a novel small molecule inhibitor of Jak 1/2, which have been shown to be key mediators of Stat3 activation. Both DW-MRI and DCE-MRI have been widely used previously to monitor cancer treatment. Jak/Stat pathway inhibition has been shown to modulate tumor cell survival and tumor angiogenesis, so this work seeks to assess the utility of DW-MRI and DCE-MRI in assessing the efficacy of AZD1480 compared to the anti-angiogenic drug cediranib at early treatment time points. The results fo this study indicate that DW-MRI is more sensitive to the effects of AZD 1480 treatment compared to DCE-MRI measurements.