Clinically Approved MRI Contrast Agents as Imaging Labels for a Porous Iron-Based MOF Nanocarrier: A Systematic Investigation in a Clinical MRI Setting

Metal-organic framework nanoparticles (MOF NPs) are a promising class of NP systems that offer versatile and tunable properties. Creating a magnetic resonance imaging (MRI)-MOF NP platform as a basis for a theranostic drug delivery system is considered an auspicious approach, as MRI is a routinely used clinical method allowing real-time imaging. So far clinically approved MRI contrast agents (CAs) have not been investigated systematically for the visualization of loading and release from MOF NPs. Here, loading and release of six clinically approved CAs from the MOF MIL-100(Fe) are investigated in a clinical MRI setting. Standard procedures, beginning with sample preparation up to MRI methods, are established for that purpose. Results are reproduced and verified by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) and thiocyanate testing. The macrocyclic CA gadoterate meglumine is identified as the best CA candidate for labeling MIL-100(Fe). The CA is successfully loaded after 1 h, and also effectively released within the first hour. The MR-active CA and iron residuals in supernatants are differentiable based on MRI only and concentrations can be successfully calculated. The presented systematic approach suggests procedures and MRI-methodology that can be used as blueprint strategy when labeling porous NPs with clinically approved MRI CAs.