title: 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.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02141 (USA); Sichuan Key Laboratory of Medical Imaging, North Sichuan Medical College, Nanchong (China).
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gale
authors.forename: Iliyana
authors.initials: I
authors.lastname: Atanasova
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Rietz
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008805:Mice, Inbred A; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; D017895:Manganese Compounds; D014443:Tyrosine; D004492:Edetic Acid
keywords: NMR spectroscopy; dendrimers; imaging agents; magnetic resonance imaging; manganese