Quantitative Mapping of Glutathione within Intracranial Tumors through Interlocked MRI Signals of a Responsive Nanoprobe

Abstract Studies reveal that malignant tumors feature uneven distributions of some key biomarkers across the entire tumorous region. Nevertheless, only very limited progress has been made towards non‐invasive and quantitative detection of tumor‐specific biomarkers in vivo, especially with clinically compatible imaging modalities. Reported here is an Fe 3 O 4 nanoparticle‐based glutathione (GSH) responsive magnetic resonance imaging (MRI) probe that can form particle aggregates within tumors in vivo to give rise to strong GSH concentration dependent interlocked relaxivities. A quantitative correlation between the interlocked MRI signals and local GSH concentration was established, and further applied for mapping the heterogeneous distribution of GSH within an intracranial tumor (2.4 mm × 1.6 mm) in vivo. This methodology will offer a practical route for quantitatively mapping tumor‐specific biomarkers in vivo with unlimited detection depth, which largely challenges optical‐imaging‐based approaches.