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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
Ijin
I
Joo
Jeong Min
JM
Lee
Joon Koo
JK
Han
Byung Ihn
BI
Choi
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D007089:Image Enhancement / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D001577:Benzophenones; C552333:N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide; D014633:Valine