고분자 조영제를 이용한 역동적 조영증강 자기공명영상의 유용성: 토끼 VX2 간암 모델에서 혈관차단제의 치료효과 평가

Abstract

Objectives: To evaluate the utility of dynamic contrast-enhanced MRI using macromolecular contrast agent (P792) for the assessment of vascular disrupting drug effect in rabbit VX2 liver tumor model. Methods: In 27 VX2 liver tumor-bearing rabbits (14 in the CKD-516 treated group and 13 in the Sorafenib treated group), DCE-MRI was performed at a 3-T scanner before and 4 hours, 24 hours after CKD-516 administration, while 7 days and 14 days after Sorafenib administration, using macromolecular MR contrast agent (P792) (n=7 and n=5) or conventional low molecular MR contrast agent (Gd-DOTA) (n=7 and n=5) in each group. Control group without Sorafenib treatment was added (n=3) in the Sorafenib treatment group. DCE-MR parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the two different MR contrast agent groups and among time points. DCE-MR parameters were correlated with histopathology of the tumor using tumor necrosis rate and microvessel density. In addition, reproducibility regarding the measurement of DCE-MRI parameters and source MR image quality was assessed and compared between the two MR contrast agent groups. Results: In the CKD-516 treated group, subgroup using macromolecular MR contrast agent showed significantly more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, compared with that using conventional MR agent. In the Sorafenib treated group, Ktrans and iAUC more decreased at 7 days and 14 days after treatment in subgroup of macromolecular MR agent than in that of conventional MR agent but without statistical significance. However, changes in DCE MR parameters did not show significant correlation with histologic parameters in both treatment groups. Inter-measurement reproducibility and overall image quality was better, but without statistical significance, in P792 group compared with Gd-DOTA group. Conclusions: DCE-MRI using macromolecular agent is more appropriate and less gadolinium-toxic in the assessment and monitoring of antivascular drug effect, than that using conventional MR contrast agent.