Development of PEGylated KMnF3nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity

Abstract

Magnetic nanoparticles consisting of manganese-based T₁-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r₁ relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF₃ nanoparticles as new T₁-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r₁ = 23.15 mM⁻¹ s⁻¹) among all the reported manganese-based T₁-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF₃ nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.