Institute of Anatomy, University of Bern, Bern, Switzerland.
Institute of Anatomy, University of Bern, Bern, Switzerland; Synchrotron Radiation for Biomedicine, INSERM UA7, 71 rue des Martyrs, 38000 Grenoble, France.
Int J Radiat Oncol Biol Phys. 2019 Dec 1;105(5):1126-1136. doi: 10.1016/j.ijrobp.2019.08.027. Epub 2019 Aug 25.
Synchrotron microbeam radiation therapy (MRT) is a method that spatially distributes the x-ray beam into several microbeams of very high dose (peak dose), regularly separated by low-dose intervals (valley dose). MRT selectively spares normal tissues, relative to conventional (uniform broad beam [BB]) radiation therapy.
To evaluate the effect of MRT on radioresistant melanoma, B16-F10 murine melanomas were implanted into mice ears. Tumors were either treated with MRT (407.6 Gy peak; 6.2 Gy valley dose) or uniform BB irradiation (6.2 Gy).
MRT induced significantly longer tumor regrowth delay than did BB irradiation. A significant 24% reduction in blood vessel perfusion was observed 5 days after MRT, and the cell proliferation index was significantly lower in melanomas treated by MRT compared with BB. MRT provoked a greater induction of senescence in melanoma cells. Bio-Plex analyses revealed enhanced concentration of monocyte-attracting chemokines in the MRT group: MCP-1 at D5, MIP-1α, MIP-1β, IL12p40, and RANTES at D9. This was associated with leukocytic infiltration at D9 after MRT, attributed mainly to CD8 T cells, natural killer cells, and macrophages.
In light of its potential to disrupt blood vessels that promote infiltration of the tumor by immune cells and its induction of senescence, MRT could be a new therapeutic approach for radioresistant melanoma.
同步辐射微束放射治疗（MRT）是一种将 X 射线束空间分布成几个高剂量（峰值剂量）微束的方法，这些微束由低剂量间隔（谷剂量）定期分隔。MRT 相对于传统的（均匀宽束 [BB]）放射治疗，可以选择性地保护正常组织。
为了评估 MRT 对耐辐射性黑色素瘤的影响，将 B16-F10 鼠黑色素瘤植入小鼠耳朵中。肿瘤要么接受 MRT（407.6 Gy 峰值；6.2 Gy 谷剂量）治疗，要么接受均匀 BB 照射（6.2 Gy）。
MRT 诱导的肿瘤再生长延迟明显长于 BB 照射。在 MRT 后 5 天观察到血管灌注显著降低 24%，并且与 BB 相比，MRT 治疗的黑色素瘤中的细胞增殖指数明显降低。MRT 可引起黑色素瘤细胞中衰老的更大诱导。Bio-Plex 分析显示，MRT 组中吸引单核细胞的趋化因子的浓度显著增加：MCP-1 在 D5 时，MIP-1α、MIP-1β、IL12p40 和 RANTES 在 D9 时。这与 MRT 后 D9 的白细胞浸润有关，主要归因于 CD8 T 细胞、自然杀伤细胞和巨噬细胞。
鉴于其破坏促进免疫细胞浸润肿瘤的血管的潜力及其诱导衰老的能力，MRT 可能是治疗耐辐射性黑色素瘤的一种新的治疗方法。
