Crokart Nathalie, Jordan Bénédicte F, Baudelet Christine, Cron Gregory O, Hotton Julie, Radermacher Kim, Grégoire Vincent, Beghein Nelson, Martinive Philippe, Bouzin Caroline, Feron Olivier, Gallez Bernard
Laboratories of Medicinal Chemistry and Radiopharmacy, Université Catholique de Louvain, B-1200 Brussels, Belgium.
Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):630-5. doi: 10.1158/1078-0432.CCR-06-0802.
We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO(2)) through inhibition of mitochondrial respiration.
The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO(2) was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO(2) (t(max), 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO(2) measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging.
All glucocorticoids tested caused a rapid increase in pO(2). At t(max), tumor perfusion decreased, indicating that the increase in pO(2) was not caused by an increase in oxygen supply. Also at t(max), global oxygen consumption decreased. When irradiation (25 Gy) was applied at t(max), the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7).
These results show the potential usefulness of the administration of glucocorticoids before irradiation.
我们推测糖皮质激素可能通过抑制线粒体呼吸增加肿瘤氧合（pO₂）来增强肿瘤放射敏感性。
研究了三种糖皮质激素（氢化可的松、地塞米松和泼尼松龙）对小鼠TLT肝肿瘤和FSaII纤维肉瘤中pO₂的影响。在pO₂达到最大值时（给药后30分钟，即t(max)），研究灌注、氧消耗和放射敏感性。使用电子顺磁共振进行局部pO₂测量。使用高频电子顺磁共振测量体内给予糖皮质激素后肿瘤细胞的氧消耗率。通过动态对比增强磁共振成像评估肿瘤灌注和通透性测量。
所有测试的糖皮质激素均导致pO₂迅速增加。在t(max)时，肿瘤灌注降低，表明pO₂的增加不是由氧供应增加引起的。同样在t(max)时，整体氧消耗降低。当在t(max)时施加照射（25 Gy）时，肿瘤放射敏感性增强（再生长延迟增加了1.7倍）。
这些结果表明照射前给予糖皮质激素具有潜在的有用性。
