Colloidally Stable Monodisperse Fe Nanoparticles as T₂ Contrast Agents for High-Field Clinical and Preclinical Magnetic Resonance Imaging

Iron nanoparticles (Fe NPs) produce negative contrast in magnetic resonance imaging (MRI) by shortening the transverse relaxation time (T2) of water protons at tissue sites. The high sensitivity of Fe toward oxidation under ambient conditions has challenged and impeded the development of stable Fe NPs for bioapplications compared to iron oxide nanoparticles (IONPs). This article demonstrates the synthesis of three batches of fairly monodisperse (size dispersion, <10%), colloidal Fe NPs with inorganic core diameters of 15.2, 12.0, and 8.8 nm. The 15.2 nm Fe NPs show high stability against oxidation, beyond 5 months, when dispersed in chloroform and deionized water. Upon dispersion in deionized water, these NPs gradually develop an amorphous iron oxide shell. On the contrary, upon transfer into water, the smaller Fe NPs oxidize to amorphous iron oxide eventually. The 15.2 nm Fe NPs exhibit much stronger shortening of the T2 relaxation time compared to the 12.0 and 8.8 nm Fe NPs at both high-field clinical 3 T and preclinical 9.4 T. The transverse relaxivity (r2) values of the 15.2 nm Fe NPs, based on per Fe ion concentration, were determined to be 167.9 mM–1 s–1 at 3 T and 236.4 mM–1 s–1 (higher than similarly sized IONPs) at 9.4 T. The respective r2/r1 ratios of 280 and 788 are high for a T2 contrast agent, although comprehensive MRI data for Fe NPs are not available in the literature for direct comparison. Fe NPs are promising MRI contrast agents for medical imaging.