title: Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial.
abstract: Nanoparticles containing high-Z elements are known to boost the efficacy of radiation therapy. Gadolinium (Gd) is particularly attractive because this element is also a positive contrast agent for MRI, which allows for the simultaneous use of imaging to guide the irradiation and to delineate the tumor. In this study, we used the Gd-based nanoparticles, AGuIX®. After intravenous injection into animals bearing B16F10 tumors, some nanoparticles remained inside the tumor cells for more than 24 hours, indicating that a single administration of nanoparticles might be sufficient for several irradiations. Combining AGuIX® with radiation therapy increases tumor cell death, and improves the life spans of animals bearing multiple brain melanoma metastases. These results provide preclinical proof-of-concept for a phase I clinical trial.
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France.
authors.forename: Shady
authors.initials: S
authors.lastname: Kotb
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France; 2. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; 3. Nano-H, St Quentin Fallavier, 38070, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Detappe
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: 4. Grenoble Institut des Neurosciences (GIN), INSERM U836, Grenoble, 38706, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Appaix
authors.affiliation: 4. Grenoble Institut des Neurosciences (GIN), INSERM U836, Grenoble, 38706, France; 5. Université Grenoble Alpes, Grenoble, France.
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France.
authors.forename: Vu-Long
authors.initials: VL
authors.lastname: Tran
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France; 3. Nano-H, St Quentin Fallavier, 38070, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Plissonneau
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France; 3. Nano-H, St Quentin Fallavier, 38070, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gehan
authors.affiliation: 6. Service de Neurochirurgie, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.affiliation: 7. Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.affiliation: 8. Radiotherapy Department, Grenoble University Hospital, 38043 Grenoble.
authors.forename: Camille
authors.initials: C
authors.lastname: Verry
authors.affiliation: 2. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.
authors.forename: Ross
authors.initials: R
authors.lastname: Berbeco
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: 1. Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne Cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy; D003287:Contrast Media / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005682:Gadolinium / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D061089:Radiotherapy, Image-Guided / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D005682:Gadolinium
keywords: AGuIX; brain metastases; imaged-guided therapy; nanoparticles; personalized medicine; radiation therapy; radiosensitizer