Bulin Anne-Laure, Broekgaarden Mans, Chaput Frédéric, Baisamy Victor, Garrevoet Jan, Busser Benoît, Brueckner Dennis, Youssef Antonia, Ravanat Jean-Luc, Dujardin Christophe, Motto-Ros Vincent, Lerouge Frédéric, Bohic Sylvain, Sancey Lucie, Elleaume Hélène
Synchrotron Radiation for Biomedical Research (STROBE) UA7 INSERM Université Grenoble Alpes Medical Beamline at the European Synchrotron Radiation Facility 71 Avenue des Martyrs Grenoble Cedex 9 38043 France.
Université de Lyon École Normale Supérieure de Lyon CNRS UMR 5182 Université Claude Bernard Lyon 1 Laboratoire de Chimie Lyon F69342 France.
Adv Sci (Weinh). 2020 Sep 7;7(20):2001675. doi: 10.1002/advs.202001675. eCollection 2020 Oct.
To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down-convert X-rays into photons with energies ranging from UV to near-infrared. During radiotherapy, these scintillating properties amplify radiation-induced damage by UV-C emission or photodynamic effects. Additionally, nanoscintillators that contain high-Z elements are likely to induce another, currently unexplored effect: radiation dose-enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X-rays by high-Z elements compared to tissues, resulting in increased production of tissue-damaging photo- and Auger electrons. In this study, Geant4 simulations reveal that rare-earth composite LaF:Ce nanoscintillators effectively generate photo- and Auger-electrons upon orthovoltage X-rays. 3D spatially resolved X-ray fluorescence microtomography shows that LaF:Ce highly concentrates in microtumors and enhances radiotherapy in an X-ray energy-dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose-enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers.
为改善胶质母细胞瘤的预后，需要创新的放射治疗方案，以增强可耐受辐射剂量的效果，同时保护周围组织。在这种背景下，纳米闪烁体作为新兴的放射治疗剂，可将X射线向下转换为能量范围从紫外线到近红外的光子。在放射治疗期间，这些闪烁特性通过紫外线-C发射或光动力效应放大辐射诱导的损伤。此外，含有高Z元素的纳米闪烁体可能会引发另一种目前尚未探索的效应：辐射剂量增强。这种现象源于高Z元素对正交电压X射线的光电吸收高于组织，从而导致产生更多对组织有损伤作用的光电子和俄歇电子。在本研究中，Geant4模拟显示，稀土复合LaF:Ce纳米闪烁体在正交电压X射线下能有效产生光电子和俄歇电子。三维空间分辨X射线荧光显微断层扫描显示，LaF:Ce高度集中在微肿瘤中，并以依赖X射线能量的方式增强放射治疗效果。在原位胶质母细胞瘤的侵袭性同基因模型中，脑内注射LaF:Ce耐受性良好，在接受单色同步加速器放射治疗的受试者中，15%实现了肿瘤完全缓解。本研究为纳米闪烁体增强辐射剂量提供了明确证据，引发了显著的放射治疗效果。总之，纳米闪烁体对于增强胶质母细胞瘤和其他抗辐射癌症放射治疗的局部损伤具有不可估量的特性。
