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

Immense studies have revealed that the malignant tumors are featured by uneven distributions of some key biomarkers across the entire tumorous region. Nevertheless, only very limited progress has been made towards non-invasive and quantitative detections of tumor-specific biomarkers in vivo, especially with clinically compatible imaging modalities. Herein, we report an Fe3O4 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 (R1 and R2). Through theoretical analysis on the basis of a number of approximations, a quantitative correlation between the interlocked MRI signals and local GSH concentration was established, which was further applied for mapping the heterogeneous distribution of GSH within an intracranial tumor (2.4 mm × 1.6 mm) in vivo. We believe our methodology will offer a potential and practical route for quantitatively mapping tumor-specific biomarkers in vivo with unlimited detection depth that largely challenges the optical-imaging-based approaches.