Dynamic contrast enhanced fluorescent molecular imaging of vascular disruption induced by combretastatin-A4P in tumor xenografts.

Dynamic contrast enhanced fluorescent molecular imaging of vascular disruption induced by combretastatin-A4P in tumor xenografts.
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DOI:
10.1166/jbn.2014.1949
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发表时间:
2014-08
影响因子:
2.9
通讯作者:
Mason RP
Mason RP
中科院分区:
工程技术3区
文献类型:
--
作者:
Liu L;Su X;Mason RP

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最近,基于吲哚菁绿色(ICG)输注后对比动力学的主成分分析(PCA),动态对比增强(DyCE)荧光成像被证明用于识别小鼠器官。我们认为,这种方法可用于评估血管破坏剂(VDA)的急性效应,因为这些药物会导致大规模血管关闭。作为原理的证明,我们已经检查了Combretastatin-A4 P(CA 4P)对在裸鼠中生长的MCF 7人乳腺肿瘤的作用。将肿瘤植入大腿中并使其生长至约7 mm直径。通过尾静脉推注给予麻醉小鼠吲哚菁绿色(ICG; 50 μl 260 μM)。使用灵敏的电荷耦合器件(CCD)相机系统在200秒内获得荧光时间过程。然后IP给予CA 4P(120 mg/kg,溶于100 μl生理盐水中),并在2小时和24小时后给予新鲜ICG后重复DyCE。在2小时时,肿瘤中产生的荧光强度大大降低,表明血管损伤,这在组织学上得到证实。24小时后,有相当大的恢复。对照小鼠和正常器官的重现性良好。我们相信该方法通过评估和优化治疗药物剂量和组合来开发VDA。
Dynamic contrast enhanced (DyCE) fluorescence imaging was recently demonstrated for identifying the organs in mice based on principal component analysis (PCA) of contrast kinetics following infusion of indocyanine green (ICG). It occurred to us that this approach could be used to evaluate acute effects of vascular disrupting agents (VDAs), since these cause massive vascular shutdown. As proof of principle, we have examined the action of combretastatin-A4P (CA4P) on MCF7 human breast tumors growing in nude mice. Tumors were implanted in the thigh and allowed to grow to about 7 mm diameter. Indocyanine green (ICG; 50 μl 260 μM) was administered as a bolus by tail vein injection to anesthetized mice. The fluorescence time course was acquired over 200 s using a sensitive charge-coupled device (CCD) camera system. CA4P was then administered IP (120 mg/kg in 100 μl saline) and DyCE repeated following administration of fresh ICG two and 24 hours later. At 2 hours the developed fluorescence intensity was much reduced in the tumors indicating vascular impairment, which was confirmed histologically. After 24 hours there was considerable recovery. Good reproducibility was found for control mice and normal organs. We believe the method shows promise for developing VDAs by evaluating and optimizing therapeutic drug doses and combinations.
2-Aryl-3-芳酰吲哚盐(OXI8007)的合成类似于Combretastatin A-4,并用作血管破坏剂。
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