Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

Abstract

Purpose: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.Conclusion: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.

Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors

“…The vascular disrupting effect of CKD-516 was previously evaluated with intravoxel incoherent motion diffusionweighted magnetic resonance imaging (MRI) or dynamic contrast-enhanced ultrasonography in a rabbit VX2 liver tumor model [ 16 , 17 ]. In our study, to observe the vascular disrupting effect of CKD-516 by dynamic contrast-enhanced MRI (DCE-MRI), 13 patients were evaluated by DCE-MRIs taken at screening and 24 hours after the first infusion of CKD-516.…”

Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

“…CKD-516 solution was prepared in 5 mL of saline at a dose of 9 mg/m 2 body surface area, which was equivalent to 0.75 mg/kg ( 10 13 14 ).…”

Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI

“…performed B-mode scanning and CEUS at baseline and after the first and second treatments. A 0.3 mL solution of sulfur hexafluoride-filled MB (SonoVue; Bracco, Milan, Italy) was injected into the tail vein, followed by 0.5 mL of a normal saline flush [19]. CEUS images were A c c e p t e d A r t i c l e acquired using a 9-MHz center-frequency linear transducer with the following parameters: dynamic range, 66; mechanical index, 0.11; gain, 22; and depth, 3 cm, equipped in an ultrasound scanner (Logiq E9; GE Healthcare, Chicago, IL, USA).…”