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.