Safety and Feasibility of Contrast-Enhanced Computed Tomography with a Nanoparticle Contrast Agent for Evaluation of Diethylnitrosamine-Induced Liver Tumors in a Rat Model

Abstract

Safety and feasibility of contrast-enhanced computed tomography (CECT) with a nanoparticulate contrast agent, ExiTron nano 12000, was evaluated in a rat liver tumor model. This study employed eighteen 8-week-old male F344 rats. Six rats given tap water for 8 weeks further divided into two: Control group and Normal Liver with CECT group. Six rats each were given tap water containing diethylnitrosamine (DEN) at 100 ppm for 8 or 14 weeks; Adenoma group and Hepatocellular carcinoma (HCC) group, respectively. Biochemical marker values and adverse events were evaluated after CT imaging. ExiTron nano 12000 was evaluated for the hepatic contrast enhancement, and the detection and measurement of liver nodules by CECT after 8- and 14-weeks administration of DEN. Post-mortem liver specimens were evaluated by hematoxylin-eosin (HE) staining, and the number and size of liver nodules were measured. The HCC group was evaluated for diagnostic concordance between HE-stained and CECT-detected nodules. The contrast agent enhanced liver and was tolerated after CECT in 15 rats. Biochemical parameter values did not differ significantly between the Control and Normal Liver groups. The numbers of CECT-detected nodules in the Adenoma and HCC groups were 14.8 ± 5.1, and 32.4 ± 8.1, respectively. The HCC group had 3.6 ± 2.7 of pathological HCCs, which were identified by CECT. The size of CECT-detected HCCs correlated significantly with that of pathological HCCs (r = 0.966, p < 0.0001). CECT with ExiTron nano 12000 is a safe and feasible method to measure tumors in a rat liver tumor model.