Hexameric Mn II Dendrimer as MRI Contrast Agent

A Mn II chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine‐derived [Mn(EDTA)(H 2 O)] 2− moieties coupled to a cyclotriphosphazene core. Variable temperature 17 O NMR spectroscopy revealed a single water co‐ligand per Mn II that undergoes fast water exchange ( k ex =(3.0±0.1)×10 8 s −1 at 37 °C). The 37 °C per Mn II relaxivity ranged from 8.2 to 3.8 m M −1 s −1 from 0.47 to 11.7 T, and is sixfold higher on a per molecule basis. From this field dependence a rotational correlation time was estimated as 0.45(±0.02) ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H 2 O)] 2− in mice at 4.7 T. On first pass, the higher per ion relaxivity of the dendrimer resulted in twofold greater blood signal than for [Gd(DTPA)(H 2 O)] 2− . Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This Mn II containing dendrimer represents a potential alternative to Gd‐based contrast agents, especially in patients with chronic kidney disease where the use of current Gd‐based agents may be contraindicated.