Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.
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DOI:
10.1016/j.jneumeth.2011.10.026
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发表时间:
2012-02-15
影响因子:
3
通讯作者:
Swartz, Harold
Swartz, Harold
中科院分区:
医学4区
文献类型:
--
作者:
Khan, Nadeem;Mupparaju, Sriram;Hou, Huagang;Williams, Benjamin B.;Swartz, Harold

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肿瘤缺氧在治疗抵抗中起着至关重要的作用。因此,肿瘤pO 2的测量可用于优化氧依赖性治疗(如放化疗)的结果。然而,潜在的优化受到缺乏在治疗期间重复和定量评估肿瘤pO 2的方法的限制,特别是在神经胶质瘤中。我们描述了原位胶质瘤pO 2的多站点电子顺磁共振(EPR)血氧饱和度的重复测量程序。这种血氧测定方法可同时测量胶质瘤和对侧脑组织中多个部位的pO 2。连续5天重复测量脑内9 L、C6、F98和U251肿瘤以及对侧脑的pO 2。9 L胶质瘤氧合良好,pO 2为27 - 36 mm Hg,而C6、F98和U251胶质瘤缺氧,pO 2为7 - 12 mm Hg。在呼吸100%O2的大鼠中研究了多部位EPR血氧测定法评估组织pO 2时间变化的潜力。在第1天和第2天观察到F98肿瘤和对侧脑pO 2显著增加,然而,胶质瘤氧合在随后的几天下降。总之,EPR血氧测定法提供了重复评估原位胶质瘤pO 2时间变化的能力。这些信息可用于测试和优化正在开发的调节肿瘤缺氧的方法。此外,EPR血氧测定法可能用于通过在神经胶质瘤pO 2增加时安排治疗来增强放化疗的结果。
Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2.
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