TITLE:
Quantitative Assessment of the Effect of Nitric Oxide Synthase Inhibition on Tumor Vascular Activity Using Dynamic Contrast-Enhanced Computed Tomography
AUTHORS:
Kenya Murase, Yoshinori Kusakabe, Shohei Miyazaki
KEYWORDS:
Nitric Oxide Synthase, N-Nitro-L-Arginine, L-Arginine, Tumor Vascular Activity, Dynamic Contrast-Enhanced Computed Tomography, Contrast Enhancement
JOURNAL NAME:
Open Journal of Medical Imaging,
Vol.6 No.2,
June
23,
2016
ABSTRACT: Purpose: The purpose of this study was to
develop a method to quantitatively assess the effect of nitric oxide synthase
(NOS) inhibition on tumor vascular activity using dynamic contrast-enhanced
computed tomography (DCE-CT) and to investigate its usefulness using animal
experiments. Mate-rials and Methods: The DCE-CT studies were performed in
anesthetized Fisher rats bearing tumors using a 4-row multi-slice CT. The
scanning started 4 s before a bolus injection of iodinated contrast agent (CA)
(150 mgI/kg) from the tail vein using an automatic injector and lasted 60 s at
1-s in-tervals. The contrast enhancement (CE) images were generated by
subtracting the CT images before and after the administration of CA. First, the
DCE-CT studies were performed before and 15, 30, and 45 min after
administration of N-nitro-L-arginine (L-NNA) (1, 3, and 10 mg/kg) or vehicle,
and the relative CE values were calculated by normalizing the CE image at each
time point by that obtained from the first DCE-CT study. Second, we investigated
the case when L-arginine (L-ARG) (200 mg/kg) and L-NNA (1, 3, and 10 mg/kg)
were administered after the first and second DCE-CT studies, respectively.
Third, we investigated the case when L-NNA (1, 3, and 10 mg/kg) and L-ARG (200
mg/kg) were administered after the first and second DCE-CT studies,
respectively. Finally, we investigated the case when L-NNA (1, 3, and 10 mg/kg)
and L-ARG (200 mg/kg) were administered simultaneously after the first DCE-CT
study. Results: The relative CE value significantly decreased after L-NNA
administration in a dose-dependent manner (p-values = 0.0074 and