Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques.
Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques.
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DOI：
10.3390/cancers12123658
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发表时间：
2020-12-05
期刊：
影响因子：
5.2
通讯作者：
Grosshans DR
中科院分区：
文献类型：
--
作者：
Bronk L;Guan F;Patel D;Ma D;Kroger B;Wang X;Tran K;Yiu J;Stephan C;Debus J;Abdollahi A;Jäkel O;Mohan R;Titt U;Grosshans DR
虽然使用质子和重离子的粒子治疗与x射线相比具有许多固有的优势，但在粒子治疗的放射生物学中仍存在许多未知因素。翔实的、高精度的生物效应数据缺乏且难以获得。本研究旨在提供一种新的高通量实验方法，以更有效地获得大量粒子治疗的生物物理数据，并将生物反应与粒子束的物理特性联系起来。为了改进现有的生物效应模型，需要大量高质量的生物物理数据，但这些数据缺乏且难以获得。本研究旨在利用一种新型的高精度、高通量实验平台，更有效地测量带电粒子束的相对生物效应（RBE）的空间分布。克隆存活被选择作为两种肺癌细胞系H460和H1437的生物学终点，用质子、碳和氦离子照射。离子特异性的多级微孔板支架被制造出来，使得96孔微孔板的每个柱在空间上沿粒子束路径位于不同的位置。使用实验验证的基于geant4的蒙特卡罗系统计算剂量，剂量平均线性能量传递（LETd）和剂量平均线性能量（yd）。细胞在海德堡离子束治疗中心（HIT）照射。实验结果表明，所有被测离子的克隆存活曲线均呈yd依赖性。在特定yd范围内，氦离子和碳离子均达到最大RBEs，然后生物功效下降，表明存在过度杀伤效应。对于质子，没有观察到过度杀伤，但RBE在布拉格峰远端增加。测量的RBE剖面强烈依赖于物理特性，如yd，并且具有离子特异性。
Although particle therapy using protons and heavier ions has many inherent advantages when compared to x-rays for cancer treatment, numerous unknowns still exist in the radiobiology of particle therapy. Informative high-accuracy biological effects data are lacking and difficult to obtain. This study aimed to provide a novel high-throughput experimental method to more efficiently obtain large amounts of biophysical data of particle therapy and to correlate the biological responses with the physical characteristics of particle beams. Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.
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