Sensitivity and Cellular Labelling Performance of Magnetically Fractionated SPIONs for Multimodal MRI/MPI Imaging

Magnetic Particle Imaging (MPI) detects superparamagnetic nanoparticles, enabling bimodal contrast with MRI. Resovist^®/Ferucarbotran, still used in research, has clinical safety compatibility but suboptimal MPI performance due to many small 5 nm SPIO cores. Magnetic fractionation can enrich larger cores, improving MPI signal and supporting cellular imaging applications. To enable bimodal MRI/MPI and assess in vivo extracellular vesicle (EV) labelling, we characterized the imaging sensitivity and cell-labelling performance of VivoTrax, a commercial formulation similar to Resovist^®, and VivoTrax Plus, obtained by magnetic fractionation. VivoTrax Plus showed higher MRI transverse relaxivity and MPI sensitivity than VivoTrax, and both formulations displayed low toxicity toward adipose-derived stem cells (ASCs). VivoTrax Plus allowed MRI detection of small cell numbers, around 100 cells, in agarose phantoms with greater sensitivity than VivoTrax. However, EVs of 30-150 nm isolated from ASCs labelled with VivoTrax Plus did not retain SPIONs, whereas EVs from VivoTrax-labelled ASCs did. Preliminary in vivo experiments in SOD-G93A mice showed MRI-detectable signal voids in the brain after intranasal EV administration, suggesting EV migration to lesioned areas. Overall, magnetic fractionation improves SPION imaging sensitivity but may alter relevant biological properties.