Multinuclear Mn(II) united-DOTA complexes with enhanced inertness and high MRI contrast ability
Multinuclear Mn(II) united-DOTA complexes with enhanced inertness and high MRI contrast ability
复制标题
DOI：
10.1016/j.xcrp.2022.100920
复制
发表时间：
2022-06
影响因子：
8.9
通讯作者：
Chengjie Sun;Zhaoxuan Yang;Peng Wu;Xiangjie Luo;Kun Liu;Binju Wang;Hongyu Lin;Jinhao Gao
中科院分区：
文献类型：
--
作者：
Chengjie Sun;Zhaoxuan Yang;Peng Wu;Xiangjie Luo;Kun Liu;Binju Wang;Hongyu Lin;Jinhao Gao
螯合不稳定性严重阻碍了基于 Mn(II) 的磁共振成像 (MRI) 造影剂的开发。在此，使用 1,4,7,10-四氮杂环十二烷-N,N',N'',N'''-四乙酸 (DOTA) 作为螯合单元，我们发现多核 Mn(II) 联合 DOTA 螯合物的惰性比临床 Gd 造影剂 Magnevis 高 69 倍。这种不寻常的惰性可归因于 Mn(II) 螯合物的多重结合，一系列对模型化合物的对照研究表明了这一点。此外，Mn(II)联合DOTA螯合物的分子纵向弛豫率比单核Mn(II)配合物高17-167倍。动态体内 MRI 实验进一步表明，与 Mn-DOTA 和 Magnevis 相比，Mn(II) 联合 DOTA 复合物可以提供更显着和更持久的对比度增强。我们的努力不仅证明了多核 Mn(II) 联合 DOTA 配合物是 Gd 基造影剂的优异替代品，而且还强调了螯合物统一作为构建高性能 Mn(II) 基造影剂的简单而强大的策略的重要性。
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. Dynamicin vivoMRI 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.