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Abstract #1538

False-Negative MRI Biomarkers of Tumour Response to Targeted Cancer Therapeutics

Jessica K.R. Boult1, Yann Jamin1, Vivien Jacobs2, Lesley D. Gilmour1, Simon Walker-Samuel1, Jane Halliday2, Paul Elvin2, Anderson J. Ryan2, John C. Waterton2, Simon P. Robinson1

1CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; 2AstraZeneca, Alderley Park, Cheshire, United Kingdom

The use of pharmacodynamic biomarkers, including imaging biomarkers, is now desirable for the evaluation of novel molecularly targeted therapeutics in oncology. Before their deployment in clinical trials, such imaging biomarkers require evaluation. Here we describe two preclinical studies in which emerging MRI biomarkers were correlated with histology to assess tumour response to Src kinase or VEGFR2 inhibition. In both studies, treatment resulted in pathological target inhibition, but the corresponding imaging biomarkers failed to show the anticipated change. Reporting of such negative preclinical imaging biomarker responses is informative for clinical trial design.