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

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 (R). 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 (R) 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.