Development of a method to quantitatively monitor the effect of inhibition of nitric oxide synthase on tumour vascular activity using dynamic contrast-enhanced computed tomography

Abstract

This study was undertaken to develop a method to quantitatively monitor the effect of inhibition of nitric oxide synthase (NOS) on tumour vascular activity using dynamic contrast-enhanced computed tomography (DCE-CT). The DCE-CT studies were performed in 13 anaesthetized rats bearing tumours. To investigate the effect of NOS inhibition, N-nitro-L-arginine (L-NNA) was intravenously administered in eight rats, while only the vehicle was administered in five rats. The contrast enhancement (CE) images were generated by subtracting the CT images before and after the administration of contrast agent. The tumour blood volume (TBV) images were also generated. The CE significantly decreased after L-NNA administration, while there were no significant changes when only the vehicle was administered. There was a good correlation between CE and TBV, suggesting that CE mainly reflects TBV. In conclusion, the present method appears to be useful for monitoring the effect of NOS inhibition on tumour vascular activity.

Keywords:

• Dynamic contrast-enhanced computed tomography
• Nitric oxide synthase
• Contrast enhancement
• Deconvolution analysis
• Angiogenesis