Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiation Physics, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany.
Center for Molecular and Cellular Bioengeneering (CMCB), DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Germany.
Radiother Oncol. 2019 Oct;139:46-50. doi: 10.1016/j.radonc.2019.06.024. Epub 2019 Jun 29.
Motivated by first animal trials showing the normal tissue protecting effect of electron and photon Flash irradiation, i.e. at mean dose rates of 100 Gy/s and higher, relative to conventional beam delivery over minutes the feasibility of proton Flash should be assessed.
A setup and beam parameter settings for the treatment of zebrafish embryo with proton Flash and proton beams of conventional dose rate were established at the University Proton Therapy Dresden. Zebrafish embryos were treated with graded doses and the differential effect on embryonic survival and the induction of morphological malformations was followed for up to four days after irradiation.
Beam parameters for the realization of proton Flash were set and tested with respect to controlled dose delivery to biological samples. Analyzing the dose dependent embryonic survival and the rate of spinal curvature as one type of developmental abnormality, no significant influence of proton dose rate was revealed. For the rate of pericardial edema as acute radiation effect, a significant difference (p < 0.05) between proton Flash and protons delivered at conventional dose rate of 5 Gy/min was observed for one dose point only.
The feasibility of Flash proton irradiation was successfully shown, whereas more experiments are required to confirm the presence or absence of a protecting effect and to figure out the limits and requirements for the Flash effect.
鉴于首次动物试验显示出电子和光子闪烁照射对正常组织的保护作用,即在 100Gy/s 及更高的平均剂量率下,相对于传统的数分钟内的束流输送,质子闪烁的可行性应进行评估。
在德累斯顿大学质子治疗中心,建立了用于治疗斑马鱼胚胎的质子闪烁和常规剂量率质子束的设备和束参数设置。用梯度剂量对斑马鱼胚胎进行处理,并在照射后长达四天的时间内,跟踪胚胎存活率的差异效应和形态畸形的诱导。
针对生物样本的受控剂量输送,设定并测试了实现质子闪烁的束参数。分析剂量依赖性胚胎存活率和脊柱弯曲率(一种发育异常类型),未发现质子剂量率的显著影响。对于急性辐射效应的心包水肿发生率,仅在一个剂量点观察到质子闪烁与常规 5Gy/min 剂量率质子之间存在显著差异(p<0.05)。
成功证明了 Flash 质子照射的可行性,然而还需要更多的实验来确认是否存在保护效应,并确定 Flash 效应的限制和要求。