Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.9092
Revised: October 19, 2013
Accepted: November 3, 2013
Published online: December 21, 2013
AIM: To explore whether the antitumor effect of a vascular disrupting agent (VDA) would be enhanced by combining with an antiangiogenic agent, and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging (DW-MRI).
METHODS: Thirty-seven rats with implanted liver tumors were randomized into the following three groups: (1) ZD6126, a kind of VDA; (2) ZDTHA, ZD6126 in combination with an antiangiogenic, thalidomide; and (3) control. Morphological DW-MRI were performed and quantified before, 4 h and 2 d after treatment. The apparent diffusion coefficient (ADC) values were calculated separately for low b values (ADClow), high b values (ADChigh) and all b values (ADCall). The tissue perfusion contribution, ADCperf, was calculated as ADClow-ADChigh. Imaging findings were finally verified by histopathology.
RESULTS: The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis. In addition to delaying tumor growth, ZDTHA caused tumor necrosis in an additive manner, which was verified by HE staining. Although both ADChigh and ADCall in the ZD6126 and ZDTHA groups were significantly higher compared to those in the control group on day 2, the entire tumor ADChigh of ZDTHA was even higher than that of ZD6126, but the significant difference was not observed for ADCall between ZDTHA and ZD6126. This indicated that the perfusion insensitive ADChigh values calculated from high b value images performed significantly better than ADCall for the monitoring of tumor necrosis on day 2. The perfusion sensitive ADCperf derived from ADClow by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADClow at 4 h. The ADCperf could provide valuable perfusion information from DW-MRI data.
CONCLUSION: The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126 and thalidomide for solid tumors.
Core tip: The combination therapy with ZD6126 and thalidomide significantly delayed liver tumor growth due to synergistic effects by inducing cumulative tumor necrosis in rodents. The apparent diffusion coefficient (ADC)high performed significantly better than ADCall for the monitoring of tumor necrosis on day 2. The ADCperf could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADClow. The ADCperf could provide valuable perfusion information from diffusion weighted magnetic resonance imaging data.