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Study of antiangiogenic drugs by fluorescence imaging and spectroscopy of a contrast agent in mice

机译:荧光造影剂和光谱法研究小鼠抗血管生成药物

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We used two fluorescence techniques based on the Indocyanine Green contrast agent to study the effectiveness of antiangionenic drugs in mice. To this purpose, the volume of the active vasculature in different tumor models implanted in mice was assessed by means of a low noise fluorescence imaging setup and by a photon counting system working in transmittance geometry. Using a first tumor model (carcinoma MDA-MB-435) we observed that mice treated with a Vascular Disrupting Agent (ZD6126) showed a reduction in fluorescence emission of the contrast agent with respect to control mice. This was a clear indication of the vascular shutdown that took place in tumors. The effectiveness of the treatment was also confirmed by histological sections. Then, in a second experiment we considered a second tumor model (carcinoma 1A9-VS1) overexpressing the Vascular Endotelial Growth Factor (VEGF121), which is used by tumor cells to promote angiogenesis. We measured the Indocyanine Green fluorescence in mice treated with an antioangiogenic drug (Avastin~TM) and in control mice. In tumors of treated mice we observed an ICG emission lower than the one detected in control mice. This demonstrated that VEGF activity was effectively blocked by the treatment with Avastin. In conclusion, ICG fluorescence provides a simple and reliable way to assess the effectiveness of vascular targeting therapies. Measurements of the fluorescence signal can be repeated every 24 hours, thus allowing oncologists to perform longitudinal studies on the same animals.
机译:我们使用了基于吲哚菁绿造影剂的两种荧光技术来研究抗血管生成药物在小鼠中的有效性。为此,通过低噪声荧光成像装置和以透射率几何结构工作的光子计数系统,评估植入小鼠的不同肿瘤模型中活性脉管系统的体积。使用第一个肿瘤模型(癌MDA-MB-435),我们观察到用血管破坏剂(ZD6126)治疗的小鼠相对于对照小鼠,造影剂的荧光发射降低。这清楚地表明了发生在肿瘤中的血管关闭。组织学切片也证实了该治疗的有效性。然后,在第二个实验中,我们考虑了过表达血管内皮生长因子(VEGF121)的第二种肿瘤模型(癌1A9-VS1),肿瘤细胞使用该模型来促进血管生成。我们在用抗血管生成药物(AvastinTM)处理的小鼠和对照小鼠中测量了吲哚菁绿荧光。在治疗小鼠的肿瘤中,我们观察到的ICG排放低于对照组小鼠。这表明通过Avastin治疗有效地阻断了VEGF活性。总之,ICG荧光提供了一种简单可靠的方法来评估血管靶向疗法的有效性。荧光信号的测量可以每24小时重复一次,因此,肿瘤学家可以对同一只动物进行纵向研究。

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