Open AccessRadiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma
Author(s) -
Bulin AnneLaure,
Broekgaarden Mans,
Chaput Frédéric,
Baisamy Victor,
Garrevoet Jan,
Busser Benoît,
Brueckner Dennis,
Youssef Antonia,
Ravanat JeanLuc,
Dujardin Christophe,
MottoRos Vincent,
Lerouge Frédéric,
Bohic Sylvain,
Sancey Lucie,
Elleaume Hélène
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202001675
Subject(s) - radioresistance , radiation therapy , nuclear medicine , glioblastoma , radiation , context (archaeology) , irradiation , cancer research , medicine , materials science , optics , physics , radiology , biology , paleontology , nuclear physics
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 3 :Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF 3 :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 3 :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.