Sodium lanthanide tungstate-based nanoparticles as bimodal contrast agents for in vivo high-field MRI and CT imaging

Abstract

Research on high-field magnetic resonance imaging (HF-MRI) has been increased in recent years, aiming to improve diagnosis accuracy by increasing the signal-to-noise ratio and hence image quality. Conventional contrast agents (CAs) have important limitations for HF-MRI, with the consequent need for the development of new CAs. Among them, the most promising alternatives are those based on Dy³⁺ or Ho³⁺ compounds. Notably, the high atomic number of lanthanide cations would bestow a high capability for X-ray attenuation to such Dy or Ho-based compounds, which would also allow them to be employed as CAs for X-ray computed tomography (CT). In this work, we have prepared uniform NaDy(WO₄)₂ and NaHo(WO₄)₂ nanoparticles (NPs), which were dispersible under conditions that mimic the physiological media and were nontoxic for cells, meeting the main requirements for their use in vivo. Both NPs exhibited satisfactory magnetic relaxivities at 9.4 T, thus making them a promising alternative to clinical CAs for HF-MRI. Furthermore, after their intravenous administration in tumor-bearing mice, both NPs exhibited significant accumulation inside the tumor at 24 h, attributable to passive targeting by the enhanced permeability and retention (EPR) effect. Therefore, our NPs are suitable for the detection of tumors through HF-MRI. Finally, NaDy(WO₄)₂ NPs showed a superior X-ray attenuation capability than iohexol (commercial CT CA), which, along with their high r₂ value, makes them suitable as the dual-probe for both HF-MRI and CT imaging, as demonstrated by in vivo experiments conducted using healthy mice.