用集落形成和细胞阻抗测定评价同步辐射微束放射治疗与常规宽束放射治疗的剂量等效性。
An evaluation of dose equivalence between synchrotron microbeam radiation therapy and conventional broad beam radiation using clonogenic and cell impedance assays.
机构信息
Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia; Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia.
Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia; William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne, Australia.
出版信息
PLoS One. 2014 Jun 19;9(6):e100547. doi: 10.1371/journal.pone.0100547. eCollection 2014.
BACKGROUND
High-dose synchrotron microbeam radiation therapy (MRT) has shown the potential to deliver improved outcomes over conventional broadbeam (BB) radiation therapy. To implement synchrotron MRT clinically for cancer treatment, it is necessary to undertake dose equivalence studies to identify MRT doses that give similar outcomes to BB treatments.
AIM
To develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays.
METHODS
The acute response of tumour and normal cell lines (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50-560 Gy) and BB (1.5-10 Gy) irradiation was investigated using clonogenic and real time cell impedance sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or 50 µm-wide planar, polychromatic kilovoltage X-ray microbeams with 200 µm peak separation. BB irradiations were performed using a Co60 teletherapy unit or a synchrotron radiation source. BB doses that would generate biological responses similar to MRT were calculated by data interpolation and verified by clonogenic and RT-CIS assays.
RESULTS
For a given cell line, MRT equivalent BB doses identified by RT-CIS/xCELLigence were similar to those identified by clonogenic assays. Dose equivalence between MRT and BB were verified in vitro in two cell lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found for example, that BB doses of 3.4±0.1 Gy and 4.40±0.04 Gy were radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic and RT-CIS assays respectively on EMT6.5ch cells.
CONCLUSION
Our data provides the first determination of biological dose equivalence between BB and MRT modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a suitable substitute for clonogenic assays. These results will be useful for the safe selection of MRT doses for future veterinary and clinical trials.
背景
高剂量同步加速器微束放射治疗（MRT）显示出比传统宽束（BB）放射治疗有更好的疗效的潜力。为了将同步加速器 MRT 临床应用于癌症治疗，有必要进行剂量等效性研究，以确定与 BB 治疗效果相当的 MRT 剂量。
目的
开发一种体外方法，使用两种不同的基于细胞的测定方法，确定 MRT 和 BB 之间的生物学剂量等效性。
方法
使用集落形成和实时细胞阻抗传感（RT-CIS）/xCELLigence 测定法，研究肿瘤和正常细胞系（EMT6.5、4T1.2、NMuMG、EMT6.5ch、4T1ch5、SaOS-2）对 MRT（50-560 Gy）和 BB（1.5-10 Gy）照射的急性反应。MRT 是使用 25 或 50 µm 宽的平面、多色千伏 X 射线微束进行的，微束峰值间隔为 200 µm。BB 照射是使用 Co60 远距离治疗机或同步辐射源进行的。通过数据插值计算出与 MRT 产生相似生物学反应的 BB 剂量，并通过集落形成和 RT-CIS 测定法进行验证。
结果
对于给定的细胞系，通过 RT-CIS/xCELLigence 确定的 MRT 等效 BB 剂量与通过集落形成测定法确定的剂量相似。在两个细胞系 EMT6.5ch 和 SaOS-2 中，通过集落形成和 RT-CIS/xCELLigence 验证了 MRT 和 BB 之间的剂量等效性。例如，我们发现对于 EMT6.5ch 细胞，BB 剂量 3.4±0.1 Gy 和 4.40±0.04 Gy 分别与微束峰值剂量 112 Gy 在放射生物学上等效，分别使用集落形成和 RT-CIS/xCELLigence 测定法。
结论
我们的数据首次确定了不同细胞系中 BB 和 MRT 模式之间的生物学剂量等效性，并确定 RT-CIS/xCELLigence 测定法是集落形成测定法的合适替代品。这些结果将有助于为未来的兽医和临床试验安全选择 MRT 剂量。
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