Theranostics 2016; 6(3):418-427. doi:10.7150/thno.14018

Research Paper

Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial

Shady Kotb1, Alexandre Detappe1,2,3, François Lux1, Florence Appaix4, Emmanuel L. Barbier4,5, Vu-Long Tran1, Marie Plissonneau1,3, Hélène Gehan1,3, Florence Lefranc6, Claire Rodriguez-Lafrasse7, Camille Verry8, Ross Berbeco2, Olivier Tillement1, Lucie Sancey1✉

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
4. Grenoble Institut des Neurosciences (GIN), INSERM U836, Grenoble, 38706, France
5. Université Grenoble Alpes, Grenoble, France
6. Service de Neurochirurgie, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium
7. Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France
8. Radiotherapy Department, Grenoble University Hospital, 38043 Grenoble.

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.

Keywords: AGuIX, radiosensitizer, radiation therapy, brain metastases, nanoparticles, imaged-guided therapy, personalized medicine

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How to cite this article:
Kotb S, Detappe A, Lux F, Appaix F, Barbier EL, Tran VL, Plissonneau M, Gehan H, Lefranc F, Rodriguez-Lafrasse C, Verry C, Berbeco R, Tillement O, Sancey L. Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial. Theranostics 2016; 6(3):418-427. doi:10.7150/thno.14018. Available from http://www.thno.org/v06p0418.htm