Diagnosis of Metastatic Breast Tumor with an Iron-Based Hydrogen-Bonded Organic Framework via <i>T</i>₂-Weighted Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) often employs contrast agents (CAs) to improve the visualization of lesions. Although iron-based oxides have been clinically approved as <i>T</i>₂ CAs, various obstacles have hindered their widespread commercial use. Consequently, there is a pressing demand for innovative <i>T</i>₂-type CAs. Herein, we synthesized an iron-based hydrogen-bonded organic framework (Fe-HOF) from Fe-TCPP and explored its potential as a <i>T</i>₂-weighted MRI CA. The Fe-HOF demonstrated a superior relaxivity (<i>r</i>₂) of 32.067 mM^-1 s^-1 and a higher <i>r</i>₂/<i>r</i>₁ ratio of 45.25 compared to Fe-TCPP. This enhancement may be attributed to the combination of the single-atom form of Fe³⁺ with its increased radius. Our findings indicate that a 6 μmol [Fe]/kg dose of Fe-HOF significantly improves lesion contrast in <i>T</i>₂-weighted MRI scans of subcutaneous tumor model mice and liver metastasis model mice of breast tumor. The simplicity of Fe-HOF' s structure ensures the absence of complex metal ions or ligands during synthesis, and the iron component can be metabolized into the endogenous iron pool, resulting in remarkable biocompatibility and biosafety. These findings pave the way for the design of novel <i>T</i>₂-weighted MRI probes tailored for cancer characterization at various stages.