Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080-4990, USA.
Magn Reson Med. 2010 Jun;63(6):1637-47. doi: 10.1002/mrm.22442.
Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density. Here, this technique is validated with direct comparisons to ex vivo micro-CT angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and vessel density by two antiangiogenic therapeutics (anti-VEGF and anti-neuropilin-1) on an HM7 colorectal tumor model. Anti-VEGF reduced blood volume by 36 +/- 3% (P < 0.0001) and vessel density by 52 +/- 3% (P < 0.0001) at 48 h posttreatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18 +/- 6% (P < 0.05) and a reduction in vessel density of 33 +/- 5% (P < 0.05) at 48 h posttreatment.
肿瘤微血管成像已成为研究血管生成和监测抗血管生成治疗的重要工具。超顺磁氧化铁对比剂可间接对血管成像，为血管生物标志物（如血管大小指数、血容量和血管密度）的定量测量提供了一种方法。本研究通过与离体 micro-CT 血管造影和组织学血管测量的直接比较对该技术进行了验证，结果显示体内血管 MRI 测量与离体结构血管测量之间存在显著相关性。本研究还展示了 MRI 血管参数的灵敏度，结合用于分割肿瘤组织的多光谱分析技术，将分析限制在存活肿瘤组织内，排除坏死区域。结果表明，这种存活肿瘤的分割提高了对两种抗血管生成治疗药物（抗-VEGF 和抗神经纤毛蛋白-1）对 HM7 结直肠肿瘤模型的血容量和血管密度的显著作用的检测灵敏度。抗-VEGF 在治疗后 48 小时降低了 36%±3%的血容量（P<0.0001）和 52%±3%的血管密度（P<0.0001）；抗神经纤毛蛋白-1 的作用强度大约减半，血容量降低了 18%±6%（P<0.05），血管密度降低了 33%±5%（P<0.05）。
