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      Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

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          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.


          Radiation dose‐enhancement induced by rare‐earth composite nanoscintillators is predicted by in silico simulations and unequivocally demonstrates in vitro in microtumor models of glioblastoma, using tunable monochromatic synchrotron radiation. Radiation dose‐enhancement ultimately elicitsa prominent radiotherapeutic effect in a syngeneic orthotopic model of aggressive glioblastoma. These results prove the strong ability of rare‐earth composite nanoscintillators to enhance the focal damage of radiotherapy.

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          Tables of X‐ray mass attenuation coefficients and mass energy‐absorption coefficients 1 keV to 20 MeV for elements Z = 1 to 92 and 48 additional substances of dosimetric interest


            Author and article information

            Adv Sci (Weinh)
            Adv Sci (Weinh)
            Advanced Science
            John Wiley and Sons Inc. (Hoboken )
            07 September 2020
            October 2020
            : 7
            : 20 ( doiID: 10.1002/advs.v7.20 )
            [ 1 ] 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
            [ 2 ] Université de Lyon École Normale Supérieure de Lyon CNRS UMR 5182 Université Claude Bernard Lyon 1 Laboratoire de Chimie Lyon F69342 France
            [ 3 ] Deutsches Elektronen‐Synchrotron DESY Notkestrasse 85 Hamburg DE‐22607 Germany
            [ 4 ] Cancer Targets and Experimental Therapeutics Institute for Advanced Biosciences Université Grenoble Alpes INSERM U1209 CNRS UMR5309 Allée des Alpes La Tronche 38700 France
            [ 5 ] Cancer Clinical Laboratory Grenoble University Hospital Grenoble 38700 France
            [ 6 ] Department Physik Universität Hamburg Luruper Chaussee 149 Hamburg 22761 Germany
            [ 7 ] Université Grenoble Alpes CEA CNRS IRIG SyMMES UMR 5819 Grenoble F‐38000 France
            [ 8 ] Institut Lumière Matière UMR5306 Université Claude Bernard Lyon 1 CNRS Villeurbanne Cedex 69622 France
            Author notes
            © 2020 The Authors. Published by Wiley‐VCH GmbH

            This is an open access article under the terms of the License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

            Page count
            Figures: 8, Tables: 1, Pages: 18, Words: 13146
            Funded by: Fondation pour la Recherche Médicale , open-funder-registry 10.13039/501100002915;
            Award ID: ARF20170938739
            Funded by: Région Auvergne Rhône‐Alpes
            Funded by: Ligue Contre le Cancer , open-funder-registry 10.13039/501100004099;
            Award ID: R19ELLEAUME
            Funded by: LABEX PRIMES
            Award ID: ANR‐11‐LABX‐0063
            Funded by: Université de Lyon , open-funder-registry 10.13039/501100011074;
            Award ID: ANR‐11‐ISEX‐0007
            Funded by: Rotary Club
            Award ID: I‐20181082 EC
            Award ID: 730872
            Funded by: ANR , open-funder-registry 10.13039/501100001665;
            Award ID: ANR‐11‐INBS‐0006
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            October 21, 2020
            Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:22.10.2020


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