RESUMO
PURPOSE: The development of magnetic resonance imaging (MRI) contrasting agents (CAs) that are safer and have a higher relaxivity than Gd(III)-based agents is a significant research topic. Herein, we propose the use of a Mn-based metal organic framework (MOF), Mn-MOF-74, characterized by a safe paramagnetic center, a coordinatively unsaturated site (CUS) for aquation, and a long rotational correlation time, endowing high relaxivity. Furthermore, biocompatibility and delivery to the tumor are generally expected for MOFs that are obtainable in the nanometer size range. PROCEDURE: Drop-wise mixing of 2,5-dihydroxyterephthalic acid (DHTP) and Mn(II) acetate yielded Mn-MOF-74 with a diameter of < 150 nm, which was then modified with 1-fivefold higher amounts of poly(ethylene glycol) (M.W. = 5000) to afford MOFs stably dispersed in water for at least 24 h. RESULTS: The longitudinal and transverse relaxivity of the PEG-modified MOF was in the range of r1 = 8.08-13.5 and r2 = 32.7-46.8 mM-1 s-1, respectively (1.0 T, 23.7-23.9 °C), being larger than those of typical Gd(III)- and Mn(II)-based CAs of single-nuclear metal complexes. The in vivo imaging of a tumor-bearing mouse clearly showed that the tumor could be readily recognized due to signal enhancement (117%) in T1-weighted images, whereas other tissues showed small signal changes. CONCLUSIONS: These results suggest that PEG-Mn-MOF-74 can be passively delivered to tumors and can act as a high-relaxivity T1 agent.
