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Abstract #2715

Response of Orthotopic PC3 Prostate Tumors to the HIF Pathway Inhibitor NSC-134754 Assessed by Diffusion Weighted MRI and Immunohistochemistry

Lauren CJ Baker1, Jessica KR Boult1, Yann Jamin1, Simon Walker-Samuel1, Margaret A. Ashcroft2, Simon P. Robinson1

1CR-UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2University College London, London, United Kingdom

The hypoxia-inducible factor pathway (HIF) is a key regulator in tumor cell adaptation to the hypoxic microenvironment. Small molecule HIF inhibitors have been identified and are currently being evaluated in vivo using non-invasive magnetic resonance (MR) methods. In this study, we show that diffusion-weighted magnetic resonance imaging (DW-MRI) can detect tumor response to the HIF pathway inhibitor NSC-134754 24h post administration in a murine orthotopic model of prostate cancer. Complimentary ex vivo histology of parameters including hypoxia, perfused vessels and necrosis further provided an insight into tumor physiology and microenvironment alterations induced by NSC-134754.