Aim: This study reports the use of gadolinium-based AGuIX nanoparticles (NPs) as a theranostic tool for both image-guided radiation therapy and radiosensitization of brain tumors. Materials & methods: Pharmacokinetics and regulatory toxicology investigations were performed on rodents. The AGuIX NPs’ tumor accumulation was studied by MRI before 6-MV irradiation. Results: AGuIX NPs exhibited a great safety profile. A single intravenous administration enabled the tumor delineation by MRI with a T₁ tumor contrast enhancement up to 24 h, and the tumor volume reduction when combined with a clinical 6-MV radiotherapy. Conclusion: This study demonstrates the efficacy and the potential of AGuIX NPs for image-guided radiation therapy, promising properties that will be assessed in the upcoming Phase I clinical trial.