Cuenod C A, Fournier L, Balvay D, Guinebretière J-M
Department of Radiology, Hôpital Européen G. Pompidou, 20 rue Leblanc, Paris, France.
Abdom Imaging. 2006 Mar-Apr;31(2):188-93. doi: 10.1007/s00261-005-0386-5.
The process of tumor neoangiogenesis plays a central role in the growth and spread of tumors. It is currently a leading theme in oncology, and many new drugs targeting the tumor neoangiogenic process are under development. Expanding tumors become hypoxic and tumor cells express transcription factors, such as the hypoxia-inducible factor (HIF), which induce the release of proangiogenic growth factors such as vascular endothelial growth factors (VEGF) and transforming growth factors that promote the formation of new capillaries by recruiting, activating, and stimulating endothelial cells. Activated endothelial cells secrete matrix metalloproteases, which degrade the basement membrane and the extracellular matrix, and adhesion receptors such as integrins alphavbeta(3), which allow their migration into the extracellular matrix toward the tumor cells. The newly grown vessels are immature and differ from normal capillaries. They are tortuous and irregular, resulting in poorly efficient perfusion, they are leaky (especially to macromolecules), and they are independent of the normal mechanisms of regulation of the capillary blood flow. Moreover, tumor microcirculation is heterogeneous. Evaluation of angiogenesis can be used as a prognostic marker to evaluate the aggressiveness of tumor and as a potential predictive marker of antiangiogenic treatment response. Histopathologic techniques of microvascular density indexes require invasive tissue sampling and need to be standardized. Hemodynamic characteristics of immature neovessels can be noninvasively assessed by dynamic contrast-enhanced magnetic resonance imaging or computed tomography. Tissue enhancement depends on arterial input function, kinetic of distribution of blood into the capillary bed, leakage across the capillary walls, and volume of the interstitial space. Pharmacodynamic models allow the evaluation of microvascular parameters of tissue blood flow, tissue blood volume, tissue interstitial volume, mean transit time, and permeability by surface of capillary wall. Methods based on dynamic contrast enhancement have been shown to correlate with conventional outcome methods such as histopathologic studies and survival. Radiologists must be convinced that, by using this emerging and promising approach, it is becoming possible to gain functional information during routine tumor imaging.
肿瘤新生血管生成过程在肿瘤的生长和扩散中起着核心作用。它是当前肿瘤学的一个主要研究方向，许多针对肿瘤新生血管生成过程的新药正在研发中。不断增大的肿瘤会出现缺氧情况，肿瘤细胞会表达转录因子，如缺氧诱导因子（HIF），其可诱导促血管生成生长因子的释放，如血管内皮生长因子（VEGF）和转化生长因子，这些因子通过募集、激活和刺激内皮细胞来促进新毛细血管的形成。活化的内皮细胞会分泌基质金属蛋白酶，其可降解基底膜和细胞外基质，还会分泌诸如整合素αvβ3等黏附受体，使内皮细胞能够向细胞外基质迁移并朝向肿瘤细胞。新生成的血管不成熟，与正常毛细血管不同。它们迂曲且不规则，导致灌注效率低下，具有渗漏性（尤其是对大分子物质），并且不受毛细血管血流正常调节机制的控制。此外，肿瘤微循环具有异质性。血管生成的评估可作为一种预后标志物，用于评估肿瘤的侵袭性，也可作为抗血管生成治疗反应的潜在预测标志物。微血管密度指数的组织病理学技术需要进行有创组织采样，且需要标准化。不成熟新生血管的血流动力学特征可通过动态对比增强磁共振成像或计算机断层扫描进行无创评估。组织增强取决于动脉输入函数、血液在毛细血管床中的分布动力学、跨毛细血管壁的渗漏以及组织间隙空间的容积。药效学模型可通过毛细血管壁表面评估组织血流、组织血容量、组织间隙容积、平均通过时间和通透性等微血管参数。基于动态对比增强的方法已被证明与组织病理学研究和生存率等传统结果评估方法相关。放射科医生必须确信，通过使用这种新兴且有前景的方法，在常规肿瘤成像过程中获取功能信息已成为可能。
