Magnetic resonance imaging in evaluating the treatment of rat liver tumor with combretastatin A-4-phosphate

The study was to establish a preclinical assessment method for vascular disrupting agents in rat liver tumor model of Walker-256 using magnetic resonance imaging(MRI) in correlation with histology and combretastatin A-4-phosphate(CA4P) to verify the reliability of the method. Twenty tumors of 10×10 mm in diameter were obtained 16 days after implantation in left liver lobes of 20 rats. Using a 1.5T MR set,T2-weighted imaging(T2WI),pre- and post-contrast T1-weighted imaging(T1WI),diffusion-weighted imaging(DWI) were acquired at baseline,24 hour ,48 hour and 72 hour after iv injection of CA4P at 10 mg/kg and vehicle in treated and control rats, respectively. Rats were sacrified after the MRI scanning and their tumors were dissected for histopathological analysis. The results showed that, relative to normal liver, the tumors appeared to be hypo-intense on T1WI,hype-rintense on T2WI,strongly hyper-intense on DWI and was enhanced with a clear border on CE-T1WI.On CE-T1WI,CA4P-treated tumors were hypo-intense in the central region relative to peripheral enhanced tumor. The tumors in CA4P-treated group showed slower growth(P<0.01),decreased signal intensity enhancement ratio(ER) (P<0.01) and increased tumor necrosis ratio(P<0.01) compared with the control group respectively. Histopathological findings showed that untreated liver masses were composed of viable tumor cells with tumoral endothelium in flat shape and without vascular thrombosis. After the treatment, Massive central necrosis and stable thrombus occurred in the tumor. The findings indicate that MRI can accurately and non-invasively reflect the therapeutic effect of CA4P on rat liver tumor. A clinical 1.5T MRI scanner with histopathology can be used as a preclinical assessment method for analyzing therapeutic effects of vascular disrupting agents.