Bussink J, Kaanders J H, Strik A M, van der Kogel A J
Department of Radiation Oncology, Joint Centre for Radiation Oncology Arnhem-Nijmegen, UMC St. Radboud, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Radiother Oncol. 2000 Oct;57(1):21-30. doi: 10.1016/s0167-8140(00)00275-9.
In head and neck cancer, addition of both carbogen breathing and nicotinamide to accelerated fractionated radiotherapy showed increased loco-regional control rates. An assay based on the measurement of changes in tumor pO(2) in response to oxygenation modification could be helpful for selecting patients for these new treatment approaches.
The fiber-optic oxygen-sensing device, OxyLite, was used to measure changes in pO(2), at a single position in tumors, after treatment with nicotinamide and carbogen in three human xenograft tumor lines with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image processing system.
At the position of pO(2) measurement, half of the tumors showed a local increase in pO(2) after nicotinamide administration. Steep increases in pO(2) were measured in most tumors during carbogen breathing although the increase was less pronounced in tumor areas with a low pre-treatment pO(2). A trend towards a faster local response to carbogen breathing for nicotinamide pre-treated tumors was found in all three lines. There were significant differences in hypoxic fractions, based on pimonidazole binding, between the three tumor lines. There was no correlation between hypoxic marker binding and the response to carbogen breathing.
Temporal changes in local pO(2) can be measured with the OxyLite. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO(2) during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was smaller and more variable. Bio-reductive hypoxic cell marker binding in combination with OxyLite pO(2) determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO(2) in specific tumor areas.
在头颈癌中,在加速分割放疗基础上加用碳合气呼吸和烟酰胺可提高局部区域控制率。一种基于测量肿瘤pO₂对氧合改变反应的检测方法可能有助于选择适合这些新治疗方法的患者。
使用光纤氧传感装置OxyLite,在三种具有不同血管结构和缺氧模式的人异种移植肿瘤模型中,测量烟酰胺和碳合气处理后肿瘤单个位置的pO₂变化。使用匹莫硝唑作为缺氧标志物,并用数字图像处理系统进行分析。
在pO₂测量位置,一半的肿瘤在给予烟酰胺后局部pO₂升高。在大多数肿瘤中,碳合气呼吸期间pO₂急剧升高,尽管在治疗前pO₂较低的肿瘤区域升高不太明显。在所有三个模型中,均发现烟酰胺预处理的肿瘤对碳合气呼吸的局部反应有更快的趋势。基于匹莫硝唑结合情况,三种肿瘤模型的缺氧分数存在显著差异。缺氧标志物结合与对碳合气呼吸的反应之间无相关性。
可使用OxyLite测量局部pO₂的时间变化。该系统用于定量氧修饰治疗的效果。在大多数肿瘤区域观察到碳合气呼吸期间pO₂迅速升高。局部测量的对烟酰胺的反应较小且更具变异性。生物还原缺氧细胞标志物结合与OxyLite pO₂测定相结合,可在微观水平提供有关肿瘤缺氧分布模式的空间信息,同时能够连续测量特定肿瘤区域pO₂的变化。