title: Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors.
abstract: OBJECTIVE
  To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model.
  
  
  METHODS
  This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation.
  
  
  RESULTS
  CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment.
  
  
  CONCLUSIONS
  Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ijin
authors.identifier: 0000-0002-1341-4072
authors.initials: I
authors.lastname: Joo
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Hoon
authors.identifier: 0000-0002-8090-7758
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong Min
authors.identifier: 0000-0003-0561-8777
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jin Woo
authors.identifier: 0000-0002-6639-8002
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Joon Koo
authors.identifier: 0000-0001-5916-5545
authors.initials: JK
authors.lastname: Han
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byung Ihn
authors.identifier: 0000-0002-5613-1881
authors.initials: BI
authors.lastname: Choi
keywords: CKD-516; Drug therapy; Liver Neoplasms; Perfusion; Ultrasonography