Al Darwish R, Staudacher A H, Li Y, Brown M P, Bezak E
Department of Medical Physics, Royal Adelaide Hospital, Adelaide 5000, Australia and School of Physical Sciences, University of Adelaide, Adelaide 5005, Australia.
Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide 5001, Australia and School of Medicine, University of Adelaide, Adelaide 5005, Australia.
Med Phys. 2016 Nov;43(11):6145. doi: 10.1118/1.4965805.
In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector.
The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM.
Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h irradiation, respectively, considering a relative biological effectiveness of alpha particles of 5.5.
The study confirmed that the Timepix detector can be used for transmission alpha particle dosimetry. If cross-calibrated using biological dosimetry, this method will give a good indication of the biological effects of alpha particles without the need for repeated biological dosimetry which is costly, time consuming, and not readily available.
在靶向放射性核素治疗中，利用能传递治疗性辐射剂量的放射性核素靶向区域肿瘤。靶向α粒子治疗（TAT）因其能够在肿瘤范围内传递高线性能量传递的α粒子而备受关注。然而，缺乏与TAT中α粒子分布相关的数据。这些数据对于更准确地估计细胞水平的吸收剂量是必需的。因此，需要一种能够估计甚至更好地确定α粒子在细胞中沉积的吸收剂量的剂量计。在本研究中，作为第一步，作者提出了一种使用A549肺癌细胞、外部α粒子发射源（镭223；Ra - 223）和Timepix像素化半导体探测器的α粒子透射剂量测定设计。
在当前工作中，研究了来自Ra - 2M源对A549肺癌细胞系的剂量传递，Ra - 223被认为是一种有吸引力的用于α粒子治疗的放射性核素。A549细胞要么未受辐照（对照），要么用位于A549细胞单层下方的Ra - 223源发射的α粒子辐照12、1、2或3小时。使用Timepix探测器确定穿过A549细胞的透射α粒子数量，并通过荧光显微镜检查以γ - H2AX焦点形式存在的DNA双链断裂（DSB）。将透射α粒子的数量与观察到的DNA DSB相关联，并估计传递的辐射剂量。此外，使用蒙特卡罗代码SRIM计算沉积剂量。
约20%的α粒子被Timepix透射并检测到。与未辐照的对照相比，α粒子辐照后γ - H2AX焦点的频率和数量显著增加。考虑到α粒子的相对生物效能为5.5，在辐照12、1、2和3小时后，传递给A549细胞的等效剂量估计分别约为0.66、1.32、2.53和3.96 Gy。
该研究证实Timepix探测器可用于透射α粒子剂量测定。如果使用生物剂量测定进行交叉校准，这种方法将很好地指示α粒子的生物效应，而无需进行成本高、耗时且不易获得的重复生物剂量测定。
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