Synchronizing Tumor Oxygen Dynamics via 19F-MRI-Guided Nanotheranostics Enables Precision Radiotherapy

Abstract The therapeutic efficacy of radiotherapy (RT) is fundamentally constrained by tumor hypoxia, a dynamic and heterogeneous feature of the tumor microenvironment that drives radioresistance and disease progression. Despite advances in oxygen-supplementation strategies, the inability to resolve and exploit temporal oxygen fluctuations limits their clinical impact. Here, we report a fluorine-19 MRI-guided nanotheranostic platform that synchronizes tumor oxygen dynamics with precision radiotherapy. Perfluorocarbon-based nanodroplets function dually as oxygen carriers and quantitative imaging probes, leveraging the linear dependence of the 19F longitudinal relaxation rate (R1) on the oxygen partial pressure (pO2) to enable noninvasive mapping of tumor oxygenation. This approach identifies a transient peak oxygenation window following administration, providing a rational basis for temporally optimized RT delivery. Synchronizing irradiation with this imaging-defined window significantly amplifies reactive oxygen species (ROS) generation and DNA double-strand breaks, resulting in enhanced tumor regression and prolonged survival. Beyond direct radiosensitization, this strategy establishes a paradigm for converting stochastic hypoxia into a controllable therapeutic variable. This work presents a framework for timing-informed, image-guided precision radiotherapy, advancing the frontier of oxygen-modulated cancer therapy.