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.