Institute of Applied Physics and Measurement Technologies, Universität der Bundeswehr München, Neubiberg, Germany.
Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany.
Sci Rep. 2024 Jan 16;14(1):1418. doi: 10.1038/s41598-024-51951-6.
FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.
FLASH 放疗可能通过质子、电子和 X 射线的超高剂量率，在保持肿瘤控制的同时，对健康组织产生显著的保护作用。FLASH 效应的关键因素可能是耗氧量、免疫系统和受照血容量，但目前尚无定论。因此，需要进一步的研究。我们使用体内小鼠耳模型研究了质子治疗中 FLASH 的保护（组织保护）作用。使用慕尼黑附近加兴的离子探针 SNAKE，用三种剂量率（Conv=0.06 Gy/s、Flash9=9.3 Gy/s 和 Flash930=930 Gy/s）对 Balb/c 小鼠的右耳进行 20 MeV 质子照射，总剂量为 23 Gy 或 33 Gy。在 180 天内测量耳厚度、脱皮和红斑综合炎症评分。在第 1 至 4 周和终末日采集血液，分析 TGF-β1、TNF-α、IL1α 和 IL1β 细胞因子。在 23 Gy 组中，不同剂量率之间的炎症反应没有差异。在 33 Gy 组中，Flash9 的耳肿胀和炎症评分分别降低了（57±12）%和（67±17）%，Flash930 降低了（40±13）%和（50±17）%，与 Conv 剂量率相比。血液中的细胞因子没有变化。然而，对受照血容量的估计表明，与使用 Flash9 或 Flash930 相比，使用 Conv 时，受照血容量增加了 100 倍。这表明血液可能在 FLASH 保护作用的潜在机制中发挥作用。
