FLASH 剂量率氦离子束：首次体外研究。

FLASH Dose Rate Helium Ion Beams: First In Vitro Investigations.

机构信息

Heidelberg Ion-Beam Therapy Center, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.

Heidelberg Ion-Beam Therapy Center, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Translational Radiation Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg, Germany; Division of Molecular and Translational Radiation Oncology, Heidelberg Faculty of Medicine, Heidelberg University Hospital, Heidelberg Ion-Beam Therapy Center, Heidelberg, Germany; German Cancer Consortium Core-Center Heidelberg, German Cancer Research Center, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, Heidelberg Institute of Radiation Oncology, National Center for Radiation Oncology, Heidelberg University and German Cancer Research Center, Heidelberg, Germany.

出版信息

Int J Radiat Oncol Biol Phys. 2021 Nov 15;111(4):1011-1022. doi: 10.1016/j.ijrobp.2021.07.1703. Epub 2021 Jul 31.

DOI:10.1016/j.ijrobp.2021.07.1703

PMID:34343608

Abstract

PURPOSE

To establish and investigate the effects of dose, linear energy transfer (LET), and O concentration on biologic response to ultrahigh dose rate (uHDR; FLASH) helium ion beams compared with standard dose rate (SDR) irradiation.

METHODS AND MATERIALS

Beam delivery settings for raster-scanned helium ions at both uHDR and SDR were tuned to achieve >100 Gy/s and ∼0.1 Gy/s, respectively. For both SDR and uHDR, plan optimization and calibration for 10 × 10-mm fields were performed to assess in vitro response at an LET range of 4.5 to 16 keV/µm. Clonogenic survival assay was conducted at doses ranging from 2 to 12 Gy in 2 human lung epithelial cell lines (A549 and H1437). Radiation-induced nuclear γH2AX foci (RIF) were assessed in both epithelial cell lines and primary human pulmonary fibroblasts.

RESULTS

Average dose rates achieved were 185 Gy/s and 0.12 Gy/s for uHDR and SDR, respectively. No differences in cellular response to SDR versus uHDR were observed for all tested doses at 21% O, and at 2 and 4 Gy at 1% O. In contrast, at 1% O and a dose threshold of ≳8 Gy cell survival was higher and correlated with reduced nuclear γH2AX RIF signal, indicating FLASH sparing effect in the investigated cell lines irradiated with uHDR compared with SDR.

CONCLUSIONS

The first uHDR delivery of raster-scanned particle beams was achieved using helium ions, reaching FLASH-level dose-rates of >100 Gy/s. Baseline oxygen levels and delivered dose (≳8 Gy) play a pivotal role, irrespective of the studied cell lines, for observation of a sparing effect for helium ions.

摘要

目的

建立并研究剂量、线性能量传递（LET）和 O 浓度对超高剂量率（uHDR；FLASH）氦离子束与标准剂量率（SDR）照射的生物学反应的影响。

方法与材料

为实现 >100 Gy/s 和 ∼0.1 Gy/s 的超高剂量率和标准剂量率，对氦离子进行扫描光栅传输时对束流传输设置进行了调整。为评估 4.5 至 16 keV/µm LET 范围内的体外反应，对 SDR 和 uHDR 进行了 10×10-mm 场的计划优化和校准。在 2 个人类肺上皮细胞系（A549 和 H1437）中，进行了 2 至 12 Gy 剂量范围内的集落形成存活测定。在这两种上皮细胞系和原代人肺成纤维细胞中评估了辐射诱导的核 γH2AX 焦点（RIF）。

结果

超高剂量率和标准剂量率的平均剂量率分别为 185 Gy/s 和 0.12 Gy/s。在 21% O 下，以及在 1% O 下的 2 和 4 Gy 时，对于所有测试剂量，SDR 与 uHDR 对细胞反应均无差异。相反，在 1% O 和 ≳8 Gy 的剂量阈值下，细胞存活率更高，与核 γH2AX RIF 信号减少相关，表明与 SDR 相比，在研究的细胞系中，用 uHDR 照射时存在 FLASH 节省效应。