Hexameric MnII Dendrimer as MRI Contrast Agent. Issue 44 (15th September 2014)

• Record Type: Journal Article
• Authors: Zhu, Jiang; Gale, Eric M.; Atanasova, Iliyana; Rietz, Tyson A.; Caravan, Peter
• Is Part Of: Chemistry. Volume 20:Issue 44(2014)
• Page Start: 14507
• Page End: 14513
• Publication Date: 2014-09-15
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201403883
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 ¹⁷O NMR spectroscopy revealed a single water co‐ligand per Mn^II that undergoes fast water exchange (<italic>k</italic>_ex=(3.0±0.1)×10⁸ s⁻¹ at 37 °C). The 37 °C per Mn^II relaxivity ranged from 8.2 to 3.8 m<sc>M</sc>⁻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)(H₂O)]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)(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.</p> </abstract>