title: Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment.
abstract: AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM®. An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM® is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection. We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.
authors.affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38000 Grenoble, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Duc
authors.affiliation: Institut UTINAM, UMR 6213 UFC-CNRS, Université de Franche-Comté, 16 route de Gray, 25030 Besançon, Cedex France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roux
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Paruta-Tuarez
authors.affiliation: Nano-H S.A.S, 2 Place de l'Europe, 38070 Saint Quentin-Fallavier, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38000 Grenoble, France.
authors.forename: Elke
authors.initials: E
authors.lastname: Brauer
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: Arthur
authors.initials: A
authors.lastname: Marais
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: Charles
authors.initials: C
authors.lastname: Truillet
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.affiliation: MATEIS, UMR 5510 INSA Lyon - CNRS, INSA Lyon, 69621 Villeurbanne, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Lyon 1 - CNRS, Team FENNEC, Université de Lyon, 69622 Villeurbanne, Cedex France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
keywords: 3–10 : Gadolinium; DOTA; MRI; Nanoparticles; Radiosensitization