Chaudhary Pankaj, Milluzzo Giuliana, McIlvenny Aodhan, Ahmed Hamad, McMurray Aaron, Maiorino Carla, Polin Kathryn, Romagnani Lorenzo, Doria Domenico, McMahon Stephen J, Botchway Stanley W, Rajeev Pattathil P, Prise Kevin M, Borghesi Marco
The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AE, Northern Ireland, United Kingdom.
Centre for Light-Matter Interactions, School of Mathematics and Physics, Queen's University Belfast, BT7 1NN, Northern Ireland, United Kingdom.
Phys Med Biol. 2023 Jan 9;68(2). doi: 10.1088/1361-6560/aca387.
Carbon is an ion species of significant radiobiological interest, particularly in view of its use in cancer radiotherapy, where its large Relative Biological Efficiency is often exploited to overcome radio resistance. A growing interest in highly pulsed carbon delivery has arisen in the context of the development of the FLASH radiotherapy approach, with recent studies carried out at dose rates of 40 Gy s. Laser acceleration methods, producing ultrashort ion bursts, can now enable the delivery of Gy-level doses of carbon ions at ultra-high dose rates (UHDRs), exceeding 10Gy s. While studies at such extreme dose rate have been carried out so far using low LET particles such as electrons and protons, the radiobiology of high-LET, UHDR ions has not yet been explored. Here, we report the first application of laser-accelerated carbon ions generated by focussing 10W cmintense lasers on 10-25 nm carbon targets, to irradiate radioresistant patient-derived Glioblastoma stem like cells (GSCs).We exposed GSCs to 1 Gy of 9.5 ± 0.5 MeV/n carbon ions delivered in a single ultra-short (∼400-picosecond) pulse, at a dose rate of 2 × 10Gy s, generated using the ASTRA GEMINI laser of the Central Laser Facility at the Rutherford Appleton Laboratory, Didcot, Oxfordshire, UK. We quantified carbon ion-induced DNA double strand break (DSB) damage using the 53BP1 foci formation assay and used 225 kVp x-rays as a reference radiation.Laser-accelerated carbon ions induced complex DNA DSB damage, as seen through persistent 53BP1 foci (11.5 ± 0.4 foci/cell/Gy) at 24 h and significantly larger foci (1.69 ± 0.07m) than x-rays induced ones (0.63 ± 0.02m). The relative foci induction value for laser-driven carbon ions relative to conventional x-rays was 3.2 ± 0.3 at 24 h post-irradiation also confirming the complex nature of the induced damage.Our study demonstrates the feasibility of radiobiology investigations at unprecedented dose rates using laser-accelerated high-LET carbon ions in clinically relevant models.
碳是一种具有重大放射生物学意义的离子种类，特别是考虑到其在癌症放射治疗中的应用，在癌症放疗中，常常利用其较大的相对生物效应来克服放射抗性。在FLASH放射治疗方法的发展背景下，人们对高脉冲碳离子束的输送越来越感兴趣，最近的研究是在40 Gy/s的剂量率下进行的。激光加速方法能够产生超短离子脉冲，现在可以实现以超过10 Gy/s的超高剂量率（UHDRs）输送Gy级剂量的碳离子。虽然到目前为止，在如此极端的剂量率下使用电子和质子等低传能线密度（LET）粒子进行了相关研究，但高LET、UHDR离子的放射生物学尚未得到探索。在此，我们报告了首次应用通过将10 W/cm强度的激光聚焦在10 - 25 nm的碳靶上产生的激光加速碳离子，来辐照源自患者的耐辐射胶质母细胞瘤干细胞样细胞（GSCs）。我们将GSCs暴露于以2×10 Gy/s的剂量率在单个超短（约400皮秒）脉冲中输送的1 Gy的9.5±0.5 MeV/n碳离子下，该碳离子束是使用位于英国牛津郡迪德科特的卢瑟福·阿普尔顿实验室中央激光设施的ASTRA GEMINI激光产生的。我们使用53BP1焦点形成试验量化碳离子诱导的DNA双链断裂（DSB）损伤，并使用225 kVp的X射线作为参考辐射。激光加速碳离子诱导了复杂的DNA DSB损伤，在24小时时可观察到持续的53BP1焦点（11.5±0.4个焦点/细胞/Gy），且焦点明显大于X射线诱导的焦点（1.69±0.07μm对比0.63±0.02μm）。在辐照后24小时，激光驱动碳离子相对于传统X射线的相对焦点诱导值为3.2±0.3，这也证实了诱导损伤的复杂性。我们的研究证明了在临床相关模型中使用激光加速的高LET碳离子以前所未有的剂量率进行放射生物学研究的可行性。
