Design of Mn(1,4-DO2A) derivatives as stable and inert contrast agents for magnetic resonance imaging
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<sub>MnL</sub> 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<sub>1/2</sub>) to around 22 hours. Its r<sub>1</sub> is measured as 2.34 and 2.20 mM<sup>-1</sup> s<sup>-1</sup> 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.
Authors
- Mauro Botta (ORCID: https://orcid.org/0000-0003-4192-355X)
- Fabio Carniato (ORCID: https://orcid.org/0000-0002-6268-1687)
- Fangfu Ye (ORCID: https://orcid.org/0000-0003-1279-105X)
- Lixiong Dai (ORCID: https://orcid.org/0000-0003-0983-2463)
- Zheng Cai (ORCID: https://orcid.org/0000-0001-8467-6478)
- Carlos Platas‐Iglesias (ORCID: https://orcid.org/0000-0002-6989-9654)
- Xinjian Ye (ORCID: https://orcid.org/0000-0003-2300-6117)
- Zhihan Yan (ORCID: https://orcid.org/0000-0001-6826-7439)
- Yinghui Ding
- Jiao Xu (ORCID: https://orcid.org/0000-0001-7659-2901)
- Yi Lü (ORCID: https://orcid.org/0000-0001-7832-3019)
- Xinzhong Ruan (ORCID: https://orcid.org/0000-0003-1301-4439)
- Weiyuan Xu
- Xinhui Xiao
- Yong Jian
- Gengshen Mo
Institutions
- Ningbo University (CN)
- Universidade da Coruña (ES)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Wenzhou University (CN)
- Wenzhou Medical University (CN)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- Zhejiang Lab (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Communications Chemistry
- Published
- 2025-07-26
- DOI
- https://doi.org/10.1038/s42004-025-01615-x
- Citations
- 2
- Primary Topic
- Lanthanide and Transition Metal Complexes
- Type
- article
- Field-Weighted Citation Impact
- 1.04
Funders
- National Natural Science Foundation of China
- Ministero dell’Istruzione, dell’Università e della Ricerca
- University of Chinese Academy of Sciences