A Contrast‐Enhanced Tri‐Modal MRI Technique for High‐Performance Hypoxia Imaging of Breast Cancer

Abstract Personalized radiotherapy strategies enabled by the construction of hypoxia‐guided biological target volumes (BTVs) can overcome hypoxia‐induced radioresistance by delivering high‐dose radiotherapy to targeted hypoxic areas of the tumor. However, the construction of hypoxia‐guided BTVs is difficult owing to lack of precise visualization of hypoxic areas. This study synthesizes a hypoxia‐responsive T 1 , T 2 , T 2 mapping tri‐modal MRI molecular nanoprobe (SPION@ND) and provides precise imaging of hypoxic tumor areas by utilizing the advantageous features of tri‐modal magnetic resonance imaging (MRI). SPION@ND exhibits hypoxia‐triggered dispersion‐aggregation structural transformation. Dispersed SPION@ND can be used for routine clinical BTV construction using T 1 ‐contrast MRI. Conversely, aggregated SPION@ND can be used for tumor hypoxia imaging assessment using T 2 ‐contrast MRI. Moreover, by introducing T 2 mapping, this work designs a novel method (adjustable threshold‐based hypoxia assessment) for the precise assessment of tumor hypoxia confidence area and hypoxia level. Eventually this work successfully obtains hypoxia tumor target and accurates hypoxia tumor target, and achieves a one‐stop hypoxia‐guided BTV construction. Compared to the positron emission tomography‐based hypoxia assessment, SPION@ND provides a new method that allows safe and convenient imaging of hypoxic tumor areas in clinical settings.