Gu Shengmei, Xue Jingyan, Xi Yan, Tang Rongbiao, Jin Wei, Chen Jia-Jian, Zhang Xi, Shao Zhi-Min, Wu Jiong
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Quant Imaging Med Surg. 2019 Mar;9(3):418-426. doi: 10.21037/qims.2019.03.09.
The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult.
To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. With these techniques, we were able to investigate the structures and density of microvessels in xenograft mouse models (n=24). Barium sulfate nanoparticles were injected into the left cardiac ventricle of the mice to allow the visualization of blood vessels.
Three-dimensional structures of microvessels were displayed with a high spatial image resolution of 20-30 µm. The density of angiogenesis and the incidence of lung metastasis were significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. Also, the density of smaller vessels (diameter <50 µm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter >100 µm) was not significantly changed.
Avastin inhibited tumor growth and lung metastasis by reducing microvessels. Additionally, synchrotron radiation (SR) techniques are useful as an additional tool for more precise quantification of angiogenesis.
微血管可视化是理解乳腺癌早期血管病变潜在机制以及制定有效治疗策略的关键步骤。然而，利用免疫组化分析乳腺癌血管生成来生成详细且可重复的数据一直颇具难度。
为了分析肿瘤生长过程中血管生成的多样性，并评估阿瓦斯汀（贝伐单抗）的抗血管生成作用，我们采用了新型X射线微血管造影术和基于第三代同步辐射的微型计算机断层扫描（SR微型CT）技术。借助这些技术，我们得以在异种移植小鼠模型（n = 24）中研究微血管的结构和密度。将硫酸钡纳米颗粒注入小鼠左心室以使血管可视化。
微血管的三维结构以20 - 30微米的高空间图像分辨率呈现。与对照组相比，接受阿瓦斯汀治疗的乳腺癌异种移植小鼠模型中血管生成密度和肺转移发生率显著降低。此外，在接受阿瓦斯汀治疗的小鼠中，较小血管（直径<50微米）的密度显著降低，而较大血管（直径>100微米）的密度无显著变化。
阿瓦斯汀通过减少微血管抑制肿瘤生长和肺转移。此外，同步辐射（SR）技术作为一种额外工具，有助于更精确地量化血管生成。
