Monodisperse Magnetite Nanoparticle Tracers for in vivo Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is a new biomedical imaging modality that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide (SPIO) nanoparticle tracer distributions. In this study, we synthesized monodisperse tracers for enhanced MPI performance and investigated both, their blood clearance time using a 25 kHz magnetic particle spectrometer (MPS), and biodistribution using a combination of quantitative T2-weighted MRI and tissue histology. In vitro and in vivo MPI performance of our magnetic nanoparticle tracers (MNTs), subject to biological constraints, were compared to commercially available SPIOs (Resovist). Monodisperse MNTs showed a 2-fold greater signal per unit mass, and 20% better spatial resolution. In vitro evaluation of tracers showed that MPI performance of our MNTs is preserved in blood, serum-rich cell-culture medium and gel; thus independent of changes in hydrodynamic volume and fluid viscosity—a critical prerequisite for in vivo MPI. In a rodent model, our MNTs circulated for 15 min—3× longer than Resovist—and supported our in vitro evaluation that MPI signal is preserved in the physiological environment. Furthermore, MRI and histology analysis showed that MNTs distribute in the reticuloendothelial system (RES) in a manner similar to clinically approved SPIO agents. MNTs demonstrating long-circulation times and optimized MPI performance show potential as angiography tracers and blood-pool agents for the emerging MPI imaging modality.