Nickel Ferrite Nanoparticles for In Vivo Multimodal Magnetic Resonance and Magnetic Particle Imaging

Magnetic nanoparticles have been at the center of biomedical research for decades, primarily for their applications in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Superparamagnetic particles, typically based on iron oxide crystals, are effective in both modalities, although each requires distinct magnetic properties for optimal performance. We investigated the performance of nanoparticles based on a nickel-substituted ferrite core and compared them to standard maghemite iron oxide nanoparticles. We synthesized γ-Fe₂O₃ and Ni _<i>x</i> Fe_2-<i>x</i> O₃ nanoparticles and coated them with a statistical copolymer poly-(<i>N</i>,<i>N</i>-dimethylacrylamide-<i>co</i>-acrylic acid). In vitro testing included X-ray diffraction (XRD), Mössbauer spectroscopy, magnetometry, magnetic resonance relaxometry, magnetic particle spectroscopy, and imaging. In vivo testing involved monitoring of nanoparticle biodistribution using MPI and MRI after intracardial application in a murine model. Mössbauer spectra suggest that the Ni-substituted nanoparticles consist of a stoichiometric NiFe₂O₄ ferrite and a poorly crystalline antiferromagnetic iron-(III) oxide-hydroxide phase. Amorphous-like impurities in Ni _<i>x</i> Fe_2-<i>x</i> O₃ nanoparticles were probably responsible for lower saturation magnetization than that of γ-Fe₂O₃ nanoparticles, as was proved by magnetometry, which led to lower <i>r</i> ₂ relaxivity. However, MPI revealed a higher signal in the spectrum and superior imaging performance of Ni _<i>x</i> Fe_2-<i>x</i> O₃ compared to γ-Fe₂O₃ particles, likely due to shorter Néél and Brownian relaxation times. Both types of nanoparticles showed similar performance in bimodal MRI/MPI imaging in vivo. They were detected in the liver immediately after application and appeared in the spleen within 24 h. Long-term localization in the lymph nodes was also observed. Substituting an iron with a nickel ion in the core altered the magnetic properties, leading to lower saturation magnetization and an increased signal in the magnetic particle spectra, which enhanced their performance in MPI. This study demonstrates that γ-Fe₂O₃ and Ni _<i>x</i> Fe_2-<i>x</i> O₃ nanoparticles are both suitable for combined MRI/MPI imaging; magnetic particle imaging provides a highly specific signal for anatomical magnetic resonance images.