Abstract #2701

Nitric Oxide Synthase Silencing by Bimodal Liposomes May Reduce Perfusion in Tumours as Assessed by DCE-MRI

Tammy Louise Kalber¹, Gavin D. Kenny¹, Nazila Kamaly^1,2, Willy Gsell³, Marzena Wylesinska-Arridge³, Leigh P. Brody¹, Andrew D. Miller², Jimmy D. Bell¹

¹Metabolic and Molecular Imaging Group, Imaging Sciences Department, MRC, Imperial College London, Hammersmith Hospital, London, United Kingdom; ²Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College London, London, United Kingdom; ³The Biological Imaging Centre, Imperial College London, London, United Kingdom

Human colon adenocarcinoma cells, transfected to overexpress inducible nitric oxide synthase (iNOS) were used to characterize the delivery of iNOS siRNA by bimodal liposomes in vitro and in vivo. Incubation in vitro resulted in a significant decrease in nitrite by day 72. Whereas, iNOS overexpressing tumours administered with iNOS siRNA liposomes resulted in decreased T₁ over 24 hours, consistent with gradual accumulation within the tumour. Tumour volume measurements showed growth restriction and regression suggestive of siRNA release resulting in gene silencing and therapeutic effect after ~ 5 days. However, DCE-MRI was not able to evaluate changes in tumour perfusion leading.