J Korean Soc Ultrasound Med.  2013 Jun;32(2):132-142.

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

• Hwang SI
• Lee HJ
• Kim KJ
• Chung JH
• Jung HS
• Jeon JJ

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.

Keyword

Ultrasonography; Contrast agent; Prostate cancer; Parametric imaging; Angiogenesis

MeSH Terms

Animals
Extremities
Humans
Mice
Mice, Nude
Models, Animal
Prostate
Prostatic Neoplasms
Transplantation, Heterologous
Tumor Burden
Vascular Endothelial Growth Factor A
Veins
Vascular Endothelial Growth Factor A