Pharmacokinetic Profiling of Unlabeled Magnetic Nanoparticles Using Magnetic Particle Imaging as a Novel Cold Tracer Assay

We present a magnetic particle imaging (MPI)-based assay for calculating the blood half-life and tissue uptake of magnetic nanoparticles (MNPs) without the need of labeling them. Dual-catheterized rats received 2.0 mg Fe of Synomag^®-D70, Synomag^®-D50, ferucarbotran, and Feraheme^® by femoral vein injection. The MPI signal of blood samples drawn from the femoral artery at various time points was then measured. Synomag^®-D70 exhibited biexponential clearance with half-lives of 3.2 and 31.2 min, Synomag^®-D50 a monoexponential clearance (<i>t</i>_1/2 = 11.4 min), ferucarbotran a biexponential clearance (<i>t</i>_1/2 = 2.4 and 10.8 min), and Feraheme^® a biexponential clearance (<i>t</i>_1/2 = 60.9 and 4.5 min). MPI of perfused tissues showed MNPs primarily localizing in the spleen, liver, and lymph nodes. Spectrophotometric/chemical iron detection proved unreliable due to residual iron from endogenous blood. The MPI assay is a sensitive and specific method for evaluating the pharmacokinetics of existing MNP formulations and those in the pipeline, with exquisite sensitivity for ultrashort half-lives.