A Protein-Corona-Free T₁–T₂ Dual-Modal Contrast Agent for Accurate Imaging of Lymphatic Tumor Metastasis

Precise nodal staging is particularly important to guide the treatments and determine the prognosis for cancer patients. However, it is still challenging to noninvasively and precisely detect in-depth tumor metastasis in lymph nodes (LNs) because of the small size and high potential of obtaining pseudopositive results. Herein, we report the rational design of a T1-T2 dual-modal MRI contrast agent for accurate imaging of tumor metastasis in LNs using gadolinium-embedded iron oxide nanoplates (GdIOP). The GdIOP were modulated with suitable size in vivo through surface functionalization by zwitterionic dopamine sulfonate (ZDS) molecules. The efficient uptake of GdIOP@ZDS nanoparticles through drainage effect because of the presence of large amount of macrophages and dendritic cells generates both T1 and T2 contrasts in LNs. In contrast, the low uptake of protein-corona-free GdIOP@ZDS nanoparticles by melanoma B16 tumor cells promises pseudocontrast imaging of potential tumor metastasis in LNs. The combination of T1 and T2 imaging modalities allows self-confirmed detection of a metastatic tumor with about 1.2 mm in the minimal dimension in LNs, which is close to the detection limit of submilimeter level of MRI scans. This study provides an efficient and noninvasive strategy to detect tumor metastasis in LNs with greatly enhanced diagnostic accuracy.