Development Of KMnF₃Nanocrystals As A New Type Of High Efficient MRI Contrast Agent

Magnetic resonance imaging (MRI) is a kind of noninvasive biomedical imagingtechnique which is widely used in clinical. In order to diagnose disease more correctly,people often introduce molecular contrast agent for enhancing image contrast ordefinition. In recent years, magnetic nanoparticles as MR contrast agents have beenrapidly achieved clinical application. In this paper, by analyzing nanoparticles’surface oxidation states we propose the possible reason for the low r1relaxivity ofcommon MnO nanoparticles and develop fluoroperovskite KMnF3nanoparticles asnew T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity(r1=23.15mM-1·s-1)among all the reported manganese-based T1-weighted contrastagents. We, for the first time, illustrate a typical example showing that the surfaceoxidation states of metal ions exposed on the nanoparticles’ surfaces are able toinfluence not only the optical, electronic, magnetic or catalytic properties but also theeffect of the magnetic resonance imaging by improving water proton longitudinalrelaxivity when applied as an MRI contrast agent.On this basis, we have also investigated the circulation, metabolism andbiodistribution characters of the PEGylated KMnF3nanoparticles when administratedto mice. Studies showed that the nanoparticular contrast agent revealed highbio-stability with bovine serum albumin in PBS buffer solution, and presentedexcellent biocompatibility (low cytotoxicity, undetectable hemolysis andhemagglutination). Meanwhile the new contrast agent possessed proper plasmaretention time (circulation half-life t1/2is approximately2h) and time-resolved MRIin the body of the administrated mice. It can be delivered into several organs in vivoand maintained in liver and kidney for about48hours as demonstrated byMn-biodistribution analysis. Those distinguishing features make it suitable to obtaincontrast-enhanced magnetic resonance imaging. Moreover, through the process ofpassive targeting delivery, the T1contrast agent clearly illuminates a brain tumor(glioma) with high contrast image and defined shape. Besides, we also found that thiscontrast agent can enhance MRI effect of blood capillary. This study demonstrates that PEGylated KMnF3nanoparticles represent a promising high efficient, lowcytotoxicity magnetic resonance contrast agent and may have clinical value.