Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-10-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202001675 |
| _version_ | 1818400272099049472 |
|---|---|
| author | Anne‐Laure Bulin Mans Broekgaarden Frédéric Chaput Victor Baisamy Jan Garrevoet Benoît Busser Dennis Brueckner Antonia Youssef Jean‐Luc Ravanat Christophe Dujardin Vincent Motto‐Ros Frédéric Lerouge Sylvain Bohic Lucie Sancey Hélène Elleaume |
| author_facet | Anne‐Laure Bulin Mans Broekgaarden Frédéric Chaput Victor Baisamy Jan Garrevoet Benoît Busser Dennis Brueckner Antonia Youssef Jean‐Luc Ravanat Christophe Dujardin Vincent Motto‐Ros Frédéric Lerouge Sylvain Bohic Lucie Sancey Hélène Elleaume |
| author_sort | Anne‐Laure Bulin |
| collection | DOAJ |
| description | Abstract 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 LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3: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 LaF3: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. |
| first_indexed | 2024-12-14T07:33:56Z |
| format | Article |
| id | doaj.art-0d109878c2e542a3b14e42c6b5bc669c |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-14T07:33:56Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-0d109878c2e542a3b14e42c6b5bc669c2022-12-21T23:11:15ZengWileyAdvanced Science2198-38442020-10-01720n/an/a10.1002/advs.202001675Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of GlioblastomaAnne‐Laure Bulin0Mans Broekgaarden1Frédéric Chaput2Victor Baisamy3Jan Garrevoet4Benoît Busser5Dennis Brueckner6Antonia Youssef7Jean‐Luc Ravanat8Christophe Dujardin9Vincent Motto‐Ros10Frédéric Lerouge11Sylvain Bohic12Lucie Sancey13Hélène Elleaume14Synchrotron 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 FranceSynchrotron 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 FranceUniversité de Lyon École Normale Supérieure de Lyon CNRS UMR 5182 Université Claude Bernard Lyon 1 Laboratoire de Chimie Lyon F69342 FranceSynchrotron 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 FranceDeutsches Elektronen‐Synchrotron DESY Notkestrasse 85 Hamburg DE‐22607 GermanyCancer Targets and Experimental Therapeutics Institute for Advanced Biosciences Université Grenoble Alpes INSERM U1209 CNRS UMR5309 Allée des Alpes La Tronche 38700 FranceDeutsches Elektronen‐Synchrotron DESY Notkestrasse 85 Hamburg DE‐22607 GermanySynchrotron 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 FranceUniversité Grenoble Alpes CEA CNRS IRIG SyMMES UMR 5819 Grenoble F‐38000 FranceInstitut Lumière Matière UMR5306 Université Claude Bernard Lyon 1 CNRS Villeurbanne Cedex 69622 FranceInstitut Lumière Matière UMR5306 Université Claude Bernard Lyon 1 CNRS Villeurbanne Cedex 69622 FranceUniversité de Lyon École Normale Supérieure de Lyon CNRS UMR 5182 Université Claude Bernard Lyon 1 Laboratoire de Chimie Lyon F69342 FranceSynchrotron 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 FranceCancer Targets and Experimental Therapeutics Institute for Advanced Biosciences Université Grenoble Alpes INSERM U1209 CNRS UMR5309 Allée des Alpes La Tronche 38700 FranceSynchrotron 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 FranceAbstract 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 LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3: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 LaF3: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.https://doi.org/10.1002/advs.202001675glioblastomananoscintillatorsradiation dose‐enhancementsynchrotron radiationX‐ray‐induced photodynamic therapy |
| spellingShingle | Anne‐Laure Bulin Mans Broekgaarden Frédéric Chaput Victor Baisamy Jan Garrevoet Benoît Busser Dennis Brueckner Antonia Youssef Jean‐Luc Ravanat Christophe Dujardin Vincent Motto‐Ros Frédéric Lerouge Sylvain Bohic Lucie Sancey Hélène Elleaume Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma Advanced Science glioblastoma nanoscintillators radiation dose‐enhancement synchrotron radiation X‐ray‐induced photodynamic therapy |
| title | Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma |
| title_full | Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma |
| title_fullStr | Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma |
| title_full_unstemmed | Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma |
| title_short | Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma |
| title_sort | radiation dose enhancement is a potent radiotherapeutic effect of rare earth composite nanoscintillators in preclinical models of glioblastoma |
| topic | glioblastoma nanoscintillators radiation dose‐enhancement synchrotron radiation X‐ray‐induced photodynamic therapy |
| url | https://doi.org/10.1002/advs.202001675 |
| work_keys_str_mv | AT annelaurebulin radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT mansbroekgaarden radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT fredericchaput radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT victorbaisamy radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT jangarrevoet radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT benoitbusser radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT dennisbrueckner radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT antoniayoussef radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT jeanlucravanat radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT christophedujardin radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT vincentmottoros radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT fredericlerouge radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT sylvainbohic radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT luciesancey radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma AT heleneelleaume radiationdoseenhancementisapotentradiotherapeuticeffectofrareearthcompositenanoscintillatorsinpreclinicalmodelsofglioblastoma |