Evaluation of tumor angiogenesis with a second-generation US contrast medium in a rat breast tumor model.
OBJECTIVE
Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.


METHODS
The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.


RESULTS
The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).


CONCLUSIONS
Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Eun Young
EY
Ko
Sang Hoon
SH
Lee
Hak Hee
HH
Kim
Sung Moon
SM
Kim
Myung Jin
MJ
Shin
Namkug
N
Kim
Gyungyub
G
Gong
D000818:Animals; D003287:Contrast Media; D005038:Ethylnitrosourea; D005260:Female; D006439:Hemodynamics; D007089:Image Enhancement; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D003287:Contrast Media; D005038:Ethylnitrosourea