Imaging of Tumor-Specific Hypoxia Dynamics and Its Significance in Radiation Biology
Imaging of Tumor-Specific Hypoxia Dynamics and Its Significance in Radiation Biology
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肿瘤特异性缺氧动态成像及其在放射生物学中的意义
DOI：
10.11323/jjmp.40.1_13
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Murali Cherukuri Krishna
中科院分区：
文献类型：
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作者：
安井 博宣;松元 慎吾;稲波 修;Murali Cherukuri Krishna
低氧是已知的与肿瘤放射抗性相关的特征。到目前为止，临床策略，以克服慢性缺氧，由于氧气扩散的限制已经设计。然而，间歇性或急性/循环缺氧（其频率范围可在每分钟几个循环至几小时之间）正受到越来越多的关注，因为已报道这种类型的缺氧通过增加促存活途径的表达对肿瘤恶性程度以及治疗抗性具有影响。因此，波动性缺氧的先验信息在临床治疗计划中可能是重要的，但复杂的动力学使得难以阐明间歇性缺氧的生物学意义。在这里，我们说明了使用脉冲电子自旋共振成像（ESRI）作为一种新的成像方法，直接监测波动的氧合，即循环缺氧移植肿瘤。ESRI和磁共振成像（MRI）的通用共振器平台提供了pO 2图，具有解剖学指导，无需位置移动。pO 2每3 min氧显像一次，可显示快速的氧波动，区分循环性缺氧和慢性缺氧。此外，我们已经研究了血管重整过程中的纵向pO 2映射与多酪氨酸激酶抑制剂舒尼替尼治疗。在抗血管生成治疗后2至4天，ESRI观察到肿瘤氧合的短暂改善和循环肿瘤缺氧的减少。在此期间，通过抗血管生成治疗改善氧合的放射治疗导致肿瘤生长的协同延迟。总之，这种ESRI技术结合MRI，可以提供一个强大的临床工具，非侵入性地检测肿瘤中的可变缺氧状态，并确定一个窗口的血管重整，以最大限度地发挥联合治疗与抗血管生成药物的效果。
Hypoxia has been known to be a feature associated with tumor radioresistance. So far, clinical strategies to overcome chronic hypoxia due to the limitation of the oxygen diffusion have been designed. However, intermittent or acute/cycling hypoxia, whose frequency can range between a few cycles per minutes to hours, is receiving increased attention, because this type of hypoxia has been reported to have an influence on tumor malignancy as well as treatment resistance via increased expression of pro-survival pathways. Therefore, a priori information on fluctuating hypoxia can be important in clinical treatment planning, but complicated dynamics makes it difficult to elucidate biological significance of intermittent hypoxia. Here, we illustrate the use of pulsed electron spin resonance imaging (ESRI) as a novel imaging method to directly monitor fluctuating oxygenation ie cycling hypoxia in transplanted tumors. A common resonator platform for both ESRI and magnetic resonance imaging (MRI) provided pO 2 maps with anatomical guidance without positional movement. Oxygen images every 3 min in pO 2 could visualize the rapid oxygen fluctuation and distinguish the cycling hypoxia and chronic hypoxia. Furthermore, we have examined the vascular renormalization process by longitudinally pO 2 mapping during treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient improvement in tumor oxygenation and the decrease of cycling tumor hypoxia were visualized by ESRI 2 to 4 days following antiangiogenic treatments. Radiation treatment during this time period of improved oxygenation by antiangiogenic therapy resulted in a synergistic delay in tumor growth. In conclusion, this ESRI technique combined with MRI, may offer a powerful clinical tool to noninvasively detect variable hypoxic status in tumors and to identify a window of vascular renormalization to maximize the effects of combination therapy with antiangiogenic drugs.