Evaluation of Tumor Angiogenesis in a Mouse PC-3 Prostate Cancer Model Using Dynamic Contrast-Enhanced Sonography

Abstract

The purpose of this study was to evaluate tumor angiogenesis in a mouse xenograft model injected with human PC-3 prostate cancer cells using contrast-enhanced sonography. Sixteen nude mice were injected with human prostate cancer cells on the back or the flank. Contrast-enhanced sonography was performed with a 5- to 12-MHz broadband linear transducer after a 500-μL bolus injection of a sonographic contrast agent composed of lipid shells and sulfur hexafluoride. Contrast-enhanced sonograms were obtained by the pulse inversion coded harmonic technique with a low mechanical index of 0.07. A region of interest was drawn to encompass the tumor, and time-intensity curves were acquired. After fitting the curve by a gamma variate function, the maximum intensity, area under the curve for up to 50 seconds, time to peak, shape parameter, and scale parameter were derived. The tumor volume, percentage of vascular endothelial growth factor expression, and CD31-positive vessel count (microvessel density) were correlated with the parameters derived from the time-intensity curve. The maximum intensity was positively correlated with the microvessel density with statistical significance (r = 0.552; P = .03). The percentage of vascular endothelial growth factor expression did not have any correlation with the parameters from the curve. Contrast-enhanced sonography can reflect tumor vascularity in a prostate cancer animal model. Sonography of tumor angiogenesis may permit functional assessment of the tumor vasculature and provide an imaging biomarker for tumor responses to antiangiogenic therapies.