The Correlations of Parameters Using Contrast Enhanced Ultrasonography in the Evaluation of Prostate Cancer Angiogenesis

ABSTRACT

PURPOSE: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. MATERIALS AND METHODS: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of 500 microL (1 x 10(8) microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec (AUC50), area under the ascending slope (AUC(in)), and area under the descending slope (AUC(out)) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. RESULTS: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), AUC50 (r=0.604, p=0.005), and AUC(out) (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and AUC50 (r=0.481, p=0.032), washin (r=0.662, p=0.001), and AUC(out) (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. CONCLUSION: MVD showed correlations with several of the kinetic parameters. CE-US has the potential for prediction of tumor vascularity in a prostate cancer animal model.