Macrocyclic Pyclen-Based Hybrid Nanoprobes for Magnetic Resonance Imaging of Sentinel Lymph Node Metastasis

The clinical diagnosis of sentinel lymph node (SLN) metastasis through contrast-enhanced magnetic resonance imaging (MRI) remains challenging. In this work, a pyclen-based amphiphilic gadolinium chelate (GdL) was developed and coassembled with DSPE-PEG2000 to form hybrid micelles for SLN metastasis imaging. The micelles exhibited high relaxivity and kinetic stability, with particle size and relaxivity adjustable by modifying the DSPE-PEG/GdL mass ratio. The DSPE-PEG/GdL micelles (15:1) displayed the highest T₁ relaxivity (23.5 Gd mM^-1 s^-1 at 1.5 T), which is 5.6-fold greater than that of Gd-DOTA, coupled with high kinetic stability. In a mouse model of breast cancer lymph node metastasis, SLN was successfully distinguished at a much lower dosage (0.75 or 1.5 mg Gd kg^-1 BW) compared to the clinical dose of 15.7 mg Gd kg^-1 BW, as evidenced by differences in MR signal intensity. Overall, the strategy of coassembling pyclen-based Gd chelates with DSPE-PEG2000 offers a feasible approach for developing effective MR probes for lymph node metastasis imaging.