Khan Nadeem, Li Hongbin, Hou Huagang, Lariviere Jean P, Gladstone David J, Demidenko Eugene, Swartz Harold M
EPR Center for Viable Systems, Dartmouth Medical School, Hanover, NH 03755, USA.
Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):878-85. doi: 10.1016/j.ijrobp.2008.10.025. Epub 2009 Jan 10.
Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO(2)) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO(2) in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry.
Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO(2) measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days.
Intracerebral 9L gliomas had a pO(2) of 30-32 mm Hg and C6 gliomas were relatively hypoxic, with a pO(2) of 12-14 mm Hg (p < 0.05). The tissue pO(2) of the contralateral brain was 40-45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO(2) of the 9L gliomas only. A significant increase in the pO(2) of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas.
These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO(2) and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO(2) could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation.
肿瘤缺氧是一个众所周知的治疗难题；然而，缺乏重复测量胶质瘤氧分压（pO₂）的方法限制了优化治疗方案的能力。我们使用一种新的且可能广泛有用的方法——多部位体内电子顺磁共振血氧测定法，报告了9.3 Gy辐射和吸入卡波金对大鼠原位9L和C6胶质瘤以及对侧脑pO₂的影响。
在同基因大鼠的左半球建立脑内9L和C6肿瘤，电子顺磁共振血氧测定法成功用于在9.3 Gy辐射后以及连续5天吸入卡波金期间重复测量组织pO₂。
脑内9L胶质瘤的pO₂为30 - 32 mmHg，C6胶质瘤相对缺氧，pO₂为12 - 14 mmHg（p < 0.05）。患有9L或C6胶质瘤的大鼠对侧脑的组织pO₂为40 - 45 mmHg。辐射仅导致9L胶质瘤的pO₂显著升高。在吸入卡波金的大鼠中，9L和C6胶质瘤的pO₂显著升高，但在9L胶质瘤的5天重复实验期间这种效应减弱。
这些结果突出了辐射（9.3 Gy）对组织pO₂的肿瘤特异性作用以及对吸入卡波金的不同反应。电子顺磁共振血氧测定法提供组织pO₂直接重复测量的能力在理解治疗期间缺氧动态方面可能具有至关重要的作用，进而可通过在肿瘤氧合改善时安排剂量来优化治疗。
