Hexameric MnII 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)(H2O)](2-) moieties coupled to a cyclotriphosphazene core. Variable temperature (ONMR)-O-17 spectroscopy revealed a single water co-ligand per Mn-II that undergoes fast water exchange (k(ex)=(3.0 +/- 0.1)x10(8)s(-1) at 37 degrees C). The 37 degrees C per Mn-II relaxivity ranged from 8.2 to 3.8mM(-1)s(-1) from 0.47 to 11.7T, 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)(H2O)](2-) in mice at 4.7T. On first pass, the higher per ion relaxivity of the dendrimer resulted in twofold greater blood signal than for [Gd(DTPA)(H2O)](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.