Forsberg F, Ro R J, Potoczek M, Liu J B, Merritt C R B, James K M, Dicker A P, Nazarian L N
Department of Radiology, Division of Diagnostic Ultrasound, Suite 763J, Main Building, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107, USA.
Ultrasonics. 2004 Apr;42(1-9):325-30. doi: 10.1016/j.ultras.2003.12.026.
In this paper, the fundamentals of tumor angiogenesis and the implications for ultrasound imaging will be described. Twenty-eight athymic nude mice were implanted with the human melanoma cell lines DB-1 or MW-9 (14 mice/group). Ultrasound contrast agents were injected in the tail veins. Power Doppler and pulse inversion harmonic imaging (PI-HI) was performed (in real time and intermittently). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between percent area stained with COX-2 and with VEGF relative to power Doppler (p<0.05) and intermittent PI-HI (p<0.05) measures of tumor neovascularity in the MW-9 and the DB-1 mice, respectively. Preliminary results from a human trial of the anti-angiogenic drug Angiostatin (Entremed, Rockville, MD) showed tumor volumes increased in two patients, while the vascularity remained virtually unchanged. Conversely, in three patients with diminished tumor volumes vascularity increased by 38%. In conclusion, contrast enhanced ultrasound imaging of tumor neovascularity may provide noninvasive markers of angiogenesis and may become a useful tool for monitoring anti-angiogenic therapies in vivo.
本文将描述肿瘤血管生成的基本原理及其对超声成像的意义。28只无胸腺裸鼠被植入人黑色素瘤细胞系DB - 1或MW - 9（每组14只小鼠）。超声造影剂经尾静脉注射。进行了功率多普勒和脉冲反转谐波成像（PI - HI）（实时和间歇性）。将超声结果与内皮细胞（CD31）、血管内皮生长因子（VEGF）和环氧合酶 - 2（COX - 2）的免疫组织化学染色结果进行比较。线性回归分析表明，在MW - 9和DB - 1小鼠中，COX - 2和VEGF染色面积百分比与肿瘤新生血管的功率多普勒测量值（p < 0.05）和间歇性PI - HI测量值（p < 0.05）之间分别存在统计学上的显著相关性。抗血管生成药物血管抑素（Entremed，罗克维尔，马里兰州）人体试验的初步结果显示，两名患者的肿瘤体积增大，而血管生成几乎没有变化。相反，在三名肿瘤体积减小的患者中，血管生成增加了38%。总之，肿瘤新生血管的超声造影增强成像可能提供血管生成的非侵入性标志物，并可能成为体内监测抗血管生成治疗的有用工具。
