Sparing of tissue by using micro-slit-beam radiation therapy reduces neurotoxicity compared with broad-beam radiation therapy.
Sparing of tissue by using micro-slit-beam radiation therapy reduces neurotoxicity compared with broad-beam radiation therapy.
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DOI：
10.1093/jrr/rrw065
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发表时间：
2017-01
影响因子：
2
通讯作者：
Sasaki R
中科院分区：
文献类型：
--
作者：
Mukumoto N;Nakayama M;Akasaka H;Shimizu Y;Osuga S;Miyawaki D;Yoshida K;Ejima Y;Miura Y;Umetani K;Kondoh T;Sasaki R
使用同步加速器产生的X射线束的微缝束放射治疗（MRT）允许极高剂量的照射。然而，MRT在中枢神经系统（CNS）使用中的毒性仍然未知。为了收集基线毒理学数据，我们评估了CNS靶向MRT后正常小鼠的死亡率。将雄性C57 BL/6 J小鼠头部固定在立体定位框架中。同步加速器X射线束辐射由SPring-8 BL 28 B2束线提供。对于MRT，将放射线输送至10 × 12 mm单向阵列中的各组小鼠，该阵列由25 μ m宽的射束组成，间隔为100、200或300 μm;另一组小鼠接受等效的宽射束放射治疗（BRT）进行比较。MRT的峰值和谷值剂量率分别为120和0.7戈伊/s。MRT的递送剂量为96-960戈伊，BRT的递送剂量为24-120戈伊。照射后90天监测死亡率。使用苏木精和伊红对脑组织进行染色以评价神经结构。通过Klüver-Barrera染色评价脱髓鞘。MRT的LD 50和LD 100分别为600戈伊和720戈伊，BRT的LD 50和LD 100分别为80戈伊和96戈伊。在MRT中，随着中心到中心射束间距从100 μm增加到300 μm，死亡率降低。皮质结构在MRT中保存良好，而BRT诱导不同程度的脑出血和脱髓鞘。MRT能够提供极高剂量的辐射，同时仍然最大限度地减少神经元死亡。受射束间距和照射剂量的影响，谷剂量可以代表MRT的重要生存因素。
Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-μm-wide beams spaced 100, 200 or 300 μm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96–960 Gy for MRT, and 24–120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver–Barrera staining. The LD50 and LD100 when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 μm to 300 μm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT.