1. Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival
- Author
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Sandrine Dufort, Géraldine Le Duc, Steven D. Chang, Lucie Sancey, Camille Verry, Stéphane Roux, Olivier Tillement, François Lux, Elke Bräuer-Krisch, Emmanuel L. Barbier, Michael Zhang, Geoffrey Appelboom, NanoH-sas, Stanford University Medical Center, Service de radiothérapie- CHU de Grenoble, CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
- Subjects
Male ,Radiation-Sensitizing Agents ,Gadolinium ,chemistry.chemical_element ,Contrast Media ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Theranostic Nanomedicine ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Glioma ,medicine ,Temozolomide ,Animals ,[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials ,Radiosensitizers ,business.industry ,Brain Neoplasms ,Contralateral hemisphere ,Washout ,General Medicine ,Chemoradiotherapy ,medicine.disease ,Magnetic Resonance Imaging ,Rats, Inbred F344 ,Rats ,9l glioma ,Neurology ,chemistry ,Theranostic ,Chemoradiation ,030220 oncology & carcinogenesis ,Nanoparticles ,Surgery ,Radiotherapy treatment ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Neurology (clinical) ,business ,Nuclear medicine ,Glioblastoma ,030217 neurology & neurosurgery ,Median survival ,medicine.drug - Abstract
International audience; We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 lM. This was compared to concentrations of 10.5 ± 9.2 lM and 62.9 ± 24.7 lM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
- Published
- 2019