Hexameric Mn(II) dendrimer as MRI contrast agent.

ABSTRACT: A Mn(II) chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine-derived [Mn(EDTA)(H2 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 (kex =(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?mM(-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)(H2 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)(H2 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.

SUBMITTER: Zhu J 

PROVIDER: S-EPMC4260332 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature