J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
Oncol Rep. 2010 Mar;23(3):685-92. doi: 10.3892/or_00000685.
4T1 mouse mammary adenocarcinomas and Caki-1 human renal cell carcinomas grown in mouse dorsal window chambers were serially treated with the vascular disrupting agent (VDA) OXi4503 and their responses compared. The real-time in vivo response was assessed using spectral imaging of microvascular hemoglobin saturation. To our knowledge this is the first use of spectral imaging technology for investigation of vascular disrupting agents. Previous research showing tumor size dependence in the treatment response to VDAs suggested that for the size of tumors used in this study only a moderate response would be observed; however, the tumors unexpectedly had very different responses to treatment. Caki-1 tumors showed little permanent vessel damage and experienced transient vessel collapse with time-dependent oxygenation changes followed by recovery starting at 6 h after treatment. Caki-1 tumors did not manifest necrotic avascular regions even after repeated treatments. These results are consistent with those obtained using other imaging modalities and histology. In contrast, similarly sized 4T1 tumors showed extensive vessel disintegration, minor vascular collapse, and a drop in tumor oxygenation up to 6 h post-treatment, after which reperfusion of collapsed vessels and extensive vascular remodeling and neovascularization of the tumor rim occurred from 8-48 h. The completely disintegrated vessels did not recover and left behind avascular and apparently necrotic regions in the tumor core. Spectral imaging appears to be a useful technique for in vivo investigation of vascular disrupting agents. The differential responses of these two tumor-types suggest that further investigation of the mechanisms of action of VDAs and individual characterization of tumor VDA-responses may be needed for optimal clinical use of these agents.
4T1 鼠乳腺腺癌和 Caki-1 人肾癌细胞在小鼠背部窗室中生长，并用血管破坏剂（VDA）OXi4503 进行连续治疗，并比较其反应。使用微血管血红蛋白饱和度的光谱成像实时评估体内实时反应。据我们所知，这是首次将光谱成像技术用于研究血管破坏剂。先前的研究表明，VDA 治疗反应与肿瘤大小有关，这表明对于本研究中使用的肿瘤大小，只会观察到中度反应；然而，肿瘤对治疗的反应出人意料地非常不同。Caki-1 肿瘤显示出很少的永久性血管损伤，并且随着时间的推移经历短暂的血管塌陷，伴有氧合变化，然后在治疗后 6 小时开始恢复。即使经过多次治疗，Caki-1 肿瘤也没有表现出坏死的无血管区域。这些结果与使用其他成像方式和组织学获得的结果一致。相比之下，大小相似的 4T1 肿瘤在治疗后 6 小时内显示出广泛的血管解体、轻微的血管塌陷和肿瘤氧合下降，之后从 8 小时到 48 小时，塌陷的血管再灌注和肿瘤边缘广泛的血管重塑和新生血管形成发生。完全解体的血管没有恢复，在肿瘤核心留下无血管和明显坏死的区域。光谱成像似乎是一种用于体内研究血管破坏剂的有用技术。这两种肿瘤类型的不同反应表明，可能需要进一步研究 VDA 的作用机制，并对肿瘤 VDA 反应进行个体特征分析，以优化这些药物的临床应用。
