首页> 外文会议>Conference on advances in optics for biotechnology, medicine and surgery XV >NONINVASIVE MONITORING OF TUMOR OXYGENATION RESPONSE TO ANTI-HYPOXIADRUG USING NEAR-INFRARED SPECTROSCOPY
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NONINVASIVE MONITORING OF TUMOR OXYGENATION RESPONSE TO ANTI-HYPOXIADRUG USING NEAR-INFRARED SPECTROSCOPY

机译:近红外光谱法的肿瘤氧合反应的非侵入性监测

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Tumor hypoxia is a characteristic feature of solid tumors, which will lead to enhanced tumor metastasis and resistance to radiation therapy. Many strategies have been proposed to increase the overall functional oxygenation and radiosensitivity of hypoxic tumors, by delivering more oxygen to the hypoxic tumor or reducing the oxygen consumption within the tumor by using anti-hypoxia agents. Preliminary data indicated that FDA approved drug papaverine could effectively reduce the mitochondrial oxygen consumption rate of human lung tumor cells (A549) in vitro and thus can reduce hypoxia-induced radiation resistance. However, the real-time tumor oxygenation response to papaverine in vivo remains to be characterized, and the optimal temporal window for delivery of radiation after anti-hypoxia therapy requires to be determined. Optical spectroscopy, particularly frequency-domain near-infrared spectroscopy (FD-NIRS), provides a new noninvasive approach for continuously monitoring tumor hypoxia in vivo. In this study, we have developed a side-firing fiber optic surface sensor and an FD-NIRS instrument with four laser wavelengths for quantifying tumor oxygenation in response to papaverine in human tumor xenograft models. Nude mice bearing subcutaneous A549 xenografts on the flank were used for tumor hypoxia study. Heathy nude mice without tumors were assigned as a control. The side-firing surface sensor was attached to the skin above the tumor or the muscle tissue on the flank of the animals. All animals were administrated with a constant flow of compressed air mixed with isoflurane throughout the experiments. 30-minute baseline measurement prior to injection, followed by 120-minute continuous measurement after injection were conducted for each animal. Intravenous tail injection of papaverine at 2 mg/kg or the same volume of 0.9% saline solution was applied to the animals. Typical results are presented in Fig. 1. The baseline measurement became stable with a small fluctuation of ±2% in ~15 minutes when the animals became fully anesthetized and breathed regularly. The slightly increase in tissue oxygenation (SO2) prior to injection was mainly due to injection preparing procedures like tail heating and injecting attempts. Significant increase in SO2 was observed for A549 tumors in response to papaverine (from -48% to~57%). SO2 reached the highest reading within 20 minutes after papaverine injection and remained at the highest for 30 minutes. In comparison, the difference in SO2 between the post papaverine injection and the baseline readings for muscle tissue was small. Similarly, the change in SO2 after saline injection for tumor-bearing mice was not obvious.
机译:肿瘤缺氧是实体瘤的特征,这将导致肿瘤转移和对放射治疗的抗性。已经提出了许多策略来增加缺氧肿瘤的整体官能氧合和放射敏感性,通过使用抗缺氧剂降低肿瘤内的氧气消耗。初步数据表明,FDA批准的药物罂粟碱可以在体外有效降低人肺肿瘤细胞(A549)的线粒体氧消耗率,从而减少缺氧诱导的抗辐射抗性。然而,对体内罂粟碱的实时肿瘤氧合反应仍然是特征,并且在抗缺氧治疗后辐射递送的最佳时间窗口需要确定。光学光谱,特别是频域近红外光谱(FD-NIR),提供了一种新的非侵入性方法,用于在体内连续监测肿瘤缺氧。在这项研究中,我们开发了一种侧面射击光纤表面传感器和具有四种激光波长的FD-NIRS仪器,用于响应人肿瘤异种移植模型中的罂粟碱来定量肿瘤氧合。在侧翼上携带皮下A549异种移植物的裸鼠用于肿瘤缺氧研究。没有肿瘤的香港裸鼠被指定为控制。侧面烧制表面传感器连接到肿瘤上方的皮肤或动物侧面上的肌肉组织。所有动物均受在整个实验中与异氟醚混合的压缩空气恒定的恒定流动。在注射之前30分钟的基线测量,然后对每只动物进行注射后的120分钟连续测量。将静脉注射猪尾注射在2mg / kg或相同体积的0.9%盐水溶液中施用于动物。典型的结果如图1所示。基线测量变得稳定,当动物完全麻醉和定期呼吸时,〜15分钟的小幅波动变得稳定。在注射之前的组织氧合(SO 2)略微增加主要是由于喷射制备程序,如尾部加热和注射尝试。对于A549肿瘤,响应于罂粟碱(从-48%至约57%),观察到SO2的显着增加。 SO2在罂粟碱注射后20分钟内达到最高读数,并保持最高30分钟。相比之下,后罂粟碱注射后的SO2差异和肌肉组织的基线读数很小。类似地,SO2后的盐水注射后的变化不明显。

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