Abstract
PURPOSE: Combretastatin A-4 disodium phosphate (CA4P) is a promising vascular disrupting agent (VDA) in clinical trials. As CA4P acts on dividing endothelial cells, we hypothesize that CA4P affects vessels of certain sizes. The aim of this study was to evaluate the effect of CA4P by the MRI-based vessel size imaging (VSI). EXPERIMENTAL DESIGN: C3H mammary carcinomas were grown to 200 mm(3) in the right rear foot of female CDF(1) mice. A control group of mice received no treatment, and a treatment group had CA4P administered intraperitoneally at a dose of 250 mg/kg. VSI was conducted on a 3 Tesla MR scanner to estimate the tumor blood volume (zeta(0)) and mean vessel radius (R). Vascularization was also estimated histologically by endothelial and Hoechst 33342 staining. RESULTS: zeta(0) and R showed different spatial heterogeneity. Tumor median and quartile values of zeta(0) were all significantly reduced by about 35% in the CA4P-treated group as compared with the control group, and the median and upper quartile of R were significantly increased. Histograms of zeta(0) and R showed a general decrease in zeta(0) following treatment, and values of R in a certain range ( approximately 20-30 mum) were decreased in the treatment group. The drug-induced change in zeta(0) was in agreement with histology and our previous dynamic contrast enhanced MRI (DCE-MRI) data. CONCLUSIONS: Tumor blood volume and mean vessel radius showed a clear response following treatment with CA4P. VSI may prove valuable in estimation of tumor angiogenesis and prediction of response to VDAs. Clin Cancer Res; 18(23); 6469-77. (c)2012 AACR.
