Multinuclear Mn(II) united-DOTA complexes with enhanced inertness and high MRI contrast ability
Chengjie Sun, Zhaoxuan Yang, Peng Wu, Xiangjie Luo, Kun Liu, Binju Wang, Hongyu Lin, Jinhao Gao
Abstract
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’’’-tetraacetic 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.