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Intravoxel incoherent motion diffusion-weighted MR imaging for monitoring the therapeutic efficacy of the vascular disrupting agent CKD-516 in rabbit VX2 liver tumors.

Radiology (2014-04-05)
Ijin Joo, Jeong Min Lee, Joon Koo Han, Byung Ihn Choi
ABSTRACT

To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance (MR) imaging in the quantitative assessment of the therapeutic efficacy of a vascular disrupting agent (VDA) (CKD-516) in rabbit VX2 liver tumors. The institutional animal care and use committee approved this study. In 21 VX2 liver tumor-bearing rabbits, IVIM DW imaging examinations were serially performed with a 3.0-T imaging unit by using 12 b values from 0 to 800 sec/mm(2). The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*) of tumors at different time points (baseline, 4 hours, 24 hours, 3 days, and 7 days after CKD-516 administration) were compared within the treated group (n = 15) by using the Friedman test as well as between the control (n = 6) and treated groups by using the Mann-Whitney test. Correlation between the change in tumor size and IVIM DW imaging parameters was analyzed by using the Spearman rank test. In the treated group, D* and f significantly decreased at 4 hours and then recovered to baseline at 24 hours, while D significantly increased at 24 hours (P < .005). All IVIM-derived parameters showed no significant differences between the control and treated groups at 3- and at 7-day follow-up. The greater decrease observed in f and fD* at 4 hours correlated with the smaller increase in tumor size during the 7 days of follow-up (ρ = 0.53 and 0.65, respectively; P < .05 for both). The therapeutic effect induced by a VDA could be effectively evaluated by using IVIM DW imaging, and f and fD* may be early predictive indicators of tumor response.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Valine, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Valine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
SAFC
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L-Valine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Valine, BioUltra, ≥99.5% (NT)
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Xylazine hydrochloride, ≥99.0% (HPLC)
Supelco
Xylazine hydrochloride, VETRANAL®, analytical standard
Valine, European Pharmacopoeia (EP) Reference Standard
Supelco
L-Valine, certified reference material, TraceCERT®
Xylazine hydrochloride, European Pharmacopoeia (EP) Reference Standard