Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI
Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI
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DOI：
10.1096/fj.07-103713
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Mason, Ralph P.
中科院分区：
文献类型：
--
作者：
Zhao, Dawen;Richer, Edmond;Mason, Ralph P.
生物发光成像(BLI)在评估小动物的长期癌症治疗方面有重要的应用。我们现在已经测试了使用BLI来评估血管干扰剂康泰素A4磷酸(CA4P)对表达荧光素酶的人乳腺癌细胞MDA-MB-231在小鼠体内作为异种移植瘤生长的急性影响的可行性。在给予荧光素底物后，光发射迅速增加，在大约6分钟后达到最大值，并在接下来的20分钟内逐渐下降。光发射的动力学具有很高的重现性；然而，在I.P.给予CA4P(120 mg/kg)，检测到的光发射减少50%~90%，达到最大值的时间明显推迟。24小时后，在进一步给予荧光素底物后，发光有所恢复。与基于顺磁性造影剂的动态增强MRI相比，Omniscan在肿瘤中显示了与先前文献一致的类似变化。组织学检查也证实了肿瘤血管灌注的关闭。我们相信，这一发现为BLI提供了一个重要的新应用，可以广泛应用于筛选有望导致肿瘤急性血管变化的新疗法。
Bioluminescence imaging (BLI) has found significant use in evaluating long-term cancer therapy in small animals. We have now tested the feasibility of using BLI to assess acute effects of the vascular disrupting agent combretastatin A4 phosphate (CA4P) on luciferase-expressing MDA-MB-231 human breast tumor cells growing as xenografts in mice. Following administration of luciferin substrate, there is a rapid increase in light emission reaching a maximum after about 6 min, which gradually decreases over the following 20 min. The kinetics of light emission are highly reproducible; however, following i.p. administration of CA4P (120 mg/kg), the detected light emission was decreased between 50 and 90%, and time to maximum was significantly delayed. Twenty-four hours later, there was some recovery of light emission following further administration of luciferin substrate. Comparison with dynamic contrast-enhanced MRI based on the paramagnetic contrast agent Omniscan showed comparable changes in the tumors consistent with the previous literature. Histology also confirmed shutdown of tumor vascular perfusion. We believe this finding provides an important novel application for BLI that could have widespread application in screening novel therapeutics expected to cause acute vascular changes in tumors.