X-ray-Sensitive Doped CaF₂-Based MRI Contrast Agents for Local Radiation Dose Measurement

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF₂ nanoparticles (NPs) doped with Eu³⁺ or Fe²⁺/Fe³⁺ ions. Free electrons generated by ionizing radiation allow the reduction of Eu³⁺, which produces a very small contrast in MRI, to Eu²⁺, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe²⁺ because it oxidizes to Fe³⁺, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu³⁺-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF₂ NPs doped with Fe²⁺/Fe³⁺ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.