Multinuclear Mn(II) united-DOTA complexes with enhanced inertness and high MRI contrast ability

Chelating lability significantly hinders the development of Mn(II)-based magnetic resonance image (MRI) contrast agents. Herein, using 1,4,7,10-tetraazacyclododecane-N,N',N ,N '-tetra-acetic acid (DOTA) as a chelating unit, we show that multinuclear Mn(II) united-DOTA chelates are of up to 69-fold higher inertness than Magnevist, a clinical Gd-based contrast agent. The unusual inertness could be ascribed to the multiplexed uniting of Mn(II) chelates, which is illustrated by a series of controlled studies on model compounds. Besides, molecular longitudinal relaxivities of Mn(II) united-DOTA chelates are 17-167 times higher than those of mononuclear Mn(II) complexes. Dynamic in vivo MRI experiments further reveal that Mn(II) united-DOTA complexes could provide more substantial and persistent contrast enhancement than both Mn-DOTA and Magnevist. Our efforts not only demonstrate that multinuclear Mn(II) united-DOTA complexes are a superior alternative to Gd-based contrast agents, but also highlight the significance of chelate unification as a simple yet powerful strategy for the construction of high-performance Mn(II)-based contrast agents.

Automated summary

In this study, multinuclear Mn(II) united-DOTA chelates are shown to have higher inertness and efficiency compared to Gd-based contrast agents. The unusual inertness is attributed to the multiplexed uniting of Mn(II) chelates, as demonstrated by controlled studies on model compounds. In vivo experiments further demonstrate that Mn(II) united-DOTA complexes provide more substantial and persistent contrast enhancement than both Mn-DOTA and Magnevist.