In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels.
In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels.
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DOI：
10.1371/journal.pone.0023492
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shalgi R
中科院分区：
文献类型：
--
作者：
Bar-Joseph H;Ben-Aharon I;Tzabari M;Tsarfaty G;Stemmer SM;Shalgi R
化疗可能在正常组织中诱导有害作用，导致器官损伤。直接血管损伤是最不典型的副作用。我们的目的是建立一个实时的，在体内的分子成像平台，用于评估阿霉素在小鼠体内的潜在血管毒性。小鼠性腺作为参考器官。在多柔比星（静脉内8 mg/kg）或紫杉醇（1.2 mg/kg）给药期间和之后，实时测量小鼠卵巢或睾丸血容量和股动脉血流量。通过超声生物显微镜（Vevo 2100）以微泡作为造影剂对卵巢血容量进行成像，而通过脉冲波多普勒超声对睾丸血容量和血流量以及股动脉血流量进行成像。卵巢和股骨微血管的可视化通过配备有共聚焦纤维显微镜（Cell-viZio）的荧光光学成像系统获得。使用微泡作为造影剂显示，阿霉素注射后3分钟卵巢血容量已减少33%（P<0.01）。多普勒超声在睾丸血容量和血流中描绘了相同的现象。股动脉血流以相同的方式受损。Cell-viZio成像描绘了多柔比星注射后大约同一时间的血管损伤模式：血管壁变得不规则，小血管中显示的荧光信号逐渐减弱。紫杉醇对血管无影响。我们建立了一个创新的高分辨率分子成像平台，适用于血管特征、动脉血流量和器官血容量的体内成像，从而能够在同一个体中长时间实时检测化疗诱导的效应。性腺和股动脉血流量的急性减少以及血管壁的损伤可能代表急性普遍性多柔比星相关血管毒性，这是器官损伤的初始事件。
Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice. Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio). Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect. We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury.
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