Design of Mn(1,4-DO2A) derivatives as stable and inert contrast agents for magnetic resonance imaging

Abstract Manganese(II) is considered a valuable alternative to gadolinium(III) in developing contrast agents (CAs) for magnetic resonance imaging (MRI). However, due to the labile nature of common Mn(II) complexes, designing ligands that enable stable and inert complexation is essential before clini...

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Main Authors: Weiyuan Xu, Zheng Cai, Fabio Carniato, Yi Lu, Xinjian Ye, Xinhui Xiao, Jiao Xu, Gengshen Mo, Yinghui Ding, Yong Jian, Xinzhong Ruan, Zhihan Yan, Fangfu Ye, Carlos Platas-Iglesias, Mauro Botta, Lixiong Dai
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01615-x
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Summary:Abstract Manganese(II) is considered a valuable alternative to gadolinium(III) in developing contrast agents (CAs) for magnetic resonance imaging (MRI). However, due to the labile nature of common Mn(II) complexes, designing ligands that enable stable and inert complexation is essential before clinical application. Mn(1,4-Et4DO2A) bearing four ethyl groups, is found to have a log K MnL as high as 17.86, together with a pMn of 7.52 at pH 7.4. Kinetically, Mn(1,4-Et4DO2A) is approximately 20 times more inert than Mn(1,4-DO2A) in the presence of a 25-fold excess of Zn(II) at pH 6.0 and 37 °C, with the incorporation of a benzoic group to one pendant arm extending the half-life time (t 1/2) to around 22 hours. Its r 1 is measured as 2.34 and 2.20 mM−1 s−1 at 310 K and 1.5 and 3.0 T, respectively, representing an approximate 50% increase compared to Mn(1,4-DO2A). Mn(1,4-Et4DO2A) shows hepatic preference in mice, and its efficacy in diagnosing orthotopic hepatocellular carcinoma (HCC) is also confirmed.
ISSN:2399-3669