Hou Huagang, Khan Nadeem, O'Hara Julia A, Grinberg Oleg Y, Dunn Jeff F, Abajian Michelle A, Wilmot Carmen M, Demidenko Eugene, Lu Shiyi, Steffen Robert P, Swartz Harold M
Department of Diagnostic Radiology, EPR Center for the Study of Viable Systems, Dartmouth Medical School, Hanover, NH, USA.
Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1503-9. doi: 10.1016/j.ijrobp.2004.12.077.
To determine quantitatively the changes in oxygenation of intracranial tumors induced by efaproxiral, an allosteric hemoglobin modifier. Efaproxiral reduces hemoglobin-oxygen binding affinity, which facilitates oxygen release from hemoglobin into surrounding tissues and potentially increases the pO(2) of the tumors.
The study was performed on 10 male Fisher 344 rats with 9L intracranial tumors. Electron paramagnetic resonance (EPR) oximetry was used to measure quantitatively the changes in the pO(2) in the tumors. Lithium phthalocyanine (LiPc) crystals were implanted in the tumors and in the normal brain tissue in the opposite hemispheres. We monitored the cerebral pO(2) starting 7 to 10 days after the tumor cells were implanted. NMR imaging determined the position and size of tumor in the brain. After an initial baseline EPR measurement, efaproxiral (150 mg/kg) was injected intravenously over 15 minutes, and measurements of tumor and normal brain oxygen tension were made alternately at 10-minute intervals for the next 60 minutes; the procedure was repeated for 6 consecutive days.
Efaproxiral significantly increased the pO(2) of both the intracranial tumors and the normal brain tissue on all days. The maximum increase was reached at 52.9 to 59.7 minutes and 54.1 to 63.2 minutes after injection, respectively. The pO(2) returned to baseline values at 106 to 126.5 minutes after treatment. The maximum tumor and normal tissue pO(2) values achieved after efaproxiral treatment from Day 1 through Day 6 ranged from 139.7 to 197.7 mm Hg and 103.0 to 135.9 mm Hg, respectively. The maximum increase in tumor tissue pO(2) values from Day 2 to Day 5 was greater than the maximum increase in normal tissue pO(2).
We obtained quantitative data on the timing and extent of efaproxiral-induced changes in the pO(2) of intracerebral 9L tumors. These results illustrate a unique and useful capability of in vivo EPR oximetry to obtain repeated noninvasive measurements of tumor oxygenation over a number of days. The information on the dynamics of tumor pO(2) after efaproxiral administration illustrates the ability of efaproxiral to increase intracranial tumor oxygenation.
定量测定变构血红蛋白修饰剂依氟普胺诱导的颅内肿瘤氧合变化。依氟普胺降低血红蛋白与氧的结合亲和力，促进氧从血红蛋白释放到周围组织中，并可能增加肿瘤的氧分压（pO₂）。
对10只患有9L颅内肿瘤的雄性Fisher 344大鼠进行了研究。采用电子顺磁共振（EPR）血氧测定法定量测量肿瘤内pO₂的变化。将锂酞菁（LiPc）晶体植入肿瘤以及对侧半球的正常脑组织中。在肿瘤细胞植入后7至10天开始监测脑内pO₂。核磁共振成像确定肿瘤在脑内的位置和大小。在进行初始基线EPR测量后，在15分钟内静脉注射依氟普胺（150 mg/kg），并在接下来的60分钟内每隔10分钟交替测量肿瘤和正常脑组织的氧张力；该过程连续重复6天。
依氟普胺在所有天数均显著提高了颅内肿瘤和正常脑组织的pO₂。分别在注射后52.9至59.7分钟和54.1至63.2分钟达到最大增幅。治疗后106至126.5分钟，pO₂恢复至基线值。从第1天到第6天依氟普胺治疗后肿瘤和正常组织的最大pO₂值分别为139.7至197.7 mmHg和103.0至135.9 mmHg。从第2天到第5天肿瘤组织pO₂值的最大增幅大于正常组织pO₂的最大增幅。
我们获得了依氟普胺诱导的脑内9L肿瘤pO₂变化的时间和程度的定量数据。这些结果说明了体内EPR血氧测定法在数天内获得肿瘤氧合的重复无创测量的独特且有用的能力。依氟普胺给药后肿瘤pO₂动态变化的信息说明了依氟普胺增加颅内肿瘤氧合的能力。
