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Abstract #0392

An MRI Investigation of the Effect of Active Site Mutant DDAH1 in C6 Glioma Xenografts in Vivo

Jessica Katherine Rowena Boult1, Simon Walker-Samuel1, Yann Jamin1, James M. Leiper2, Guy St.John Whitley3, Simon P. Robinson1

1CRUK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom; 2MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom; 3Department of Basic Medical Sciences, St. Georges, University of London, London, United Kingdom

Dimethylarginine dimethylaminohydrolase (DDAH) metabolizes the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine (ADMA), indirectly leading to an increase in nitric oxide. Diffusion-weighted and dynamic contract enhanced MRI were used to evaluate the vascular phenotypes of C6 glioma xenografts overexpressing either wildtype DDAH1 or an active site mutant DDAH1 incapable of metabolizing ADMA. Tumours expressing mDDAH1 demonstrated an intermediate phenotype between control and wtDDAH1 expressing tumours. Differences in ADC and native T1 and T2 times were consistent with higher cellularity/lower necrosis in the DDAH1 expressing tumours. Despite differences in VEGF expression and perfusion, no significant alterations in Ktrans or ve were observed between the 3 tumour groups.