Stepwise Purification of Superparamagnetic Iron Oxide Nanoparticles Improves Magnetic Particle Imaging Performance

Superparamagnetic iron oxide nanoparticles (SPIONs) are essential tracers for magnetic particle imaging (MPI), yet commercial formulations offer a suboptimal performance. While SPIONs are commonly synthesized via coprecipitation, thermal decomposition can produce higher-quality particles with uniform sizes and tunable morphologies, despite requiring more complex organometallic synthesis. Most tracer development prioritizes synthetic optimization, overlooking simpler yet impactful strategies. We here report a stepwise washing method applied during iron(III) oleate precursor preparation and nanoparticle synthesis that tailored the particle shape and improved the SPION performance. Compared to the commercial tracers Resovist and Perimag, our best formulation displays enhanced MPI performance, with an up to 8-fold higher signal-to-noise ratio (SNR) <i>in vitro</i> and 3-fold greater dynamic SNR <i>in vivo</i>, along with superior spatial resolution and an adequate bioaccumulation profile. Our findings establish stepwise purification as a simple yet powerful method to engineer high-performance SPIONs for supporting ongoing efforts to translate MPI to the clinic.