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Abstract #0152

Chronic Dosing with MLN0518 (Tandutinib), a Small Molecule PDGFRα/β Inhibitor, Reduces Tumour Growth, Hypoxia, and Perfusion in C6 Glioma Xenografts: An Investigation Using Susceptibility Contrast Enhanced MRI and Immunohistochemical Methods

Jessica Katherine Rowena Boult1, Simon Walker-Samuel1, Daniel P. Bradley2, Simon P. Robinson1

1CRUK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom; 2Imaging Sciences Group, Millennium: The Takeda Oncology Company, Cambridge, MA, United States

In this study, susceptibility MRI with ultra-small paramagnetic iron oxide (USPIO) and immunohistochemical methods were used to evaluate vascular and hypoxic response of C6 glioma xenografts to chronic treatment with MLN0518, a small molecule PDGFRα/β inhibitor. MLN0518 chronically limits the growth of C6 xenografts and reduces both the mean perfused vessel fraction and hypoxic area. No significant alteration in VSI, fractional blood volume or ADC were observed by MRI following 10 days treatment. These results are consistent with histological vessel measurements and quantification of necrosis, neither of which altered at this timepoint.