Single-point mutated lanmodulin as a high-performance MRI contrast agent for vascular and kidney imaging
Magnetic resonance imaging contrast agents can enhance diagnostic precision but often face limitations such as short imaging windows, low tissue specificity, suboptimal contrast enhancement, or potential toxicity, which affect resolution and long-term monitoring. Here, we present a protein contrast agent based on lanmodulin, engineered with a single-point mutation at position 108 from N to D to yield maximum gadolinium binding sites. After loading with Gd<sup>3+</sup> ions, the resulting protein complex, LanND-Gd, exhibits efficient renal clearance, high relaxivity, and prolonged renal retention compared to commercial agents. LanND-Gd enables high-performance visualization of whole-body structures and brain vasculature in male mice at a resolution finer than one hundred micrometers. In male ischemia mouse models, LanND-Gd also improves kidney dysfunction monitoring while minimizing risks of neural toxicity or immunogenic reactions. This protein-based contrast agent offers superior image quality, improved biocompatibility, and extended imaging timeframes, promising significant advancements in magnetic resonance-based diagnostics and patient outcomes.
Authors
- Hairong Zheng (ORCID: https://orcid.org/0000-0002-8558-5102)
- Hui Jun Ting (ORCID: https://orcid.org/0000-0002-5054-6680)
- Zichao Luo (ORCID: https://orcid.org/0000-0001-9236-9160)
- Suet Yen Chong (ORCID: https://orcid.org/0000-0002-3627-4025)
- Yuanyuan He (ORCID: https://orcid.org/0009-0006-5043-6349)
- Jiong‐Wei Wang (ORCID: https://orcid.org/0000-0001-7986-6082)
- Zhigao Yi (ORCID: https://orcid.org/0000-0003-0853-2055)
- Jingyu Tang (ORCID: https://orcid.org/0000-0002-5694-3783)
- Xinyi Qi (ORCID: https://orcid.org/0000-0001-6002-4782)
- Xiaogang Liu (ORCID: https://orcid.org/0000-0003-2517-5790)
- Chao Chang (ORCID: https://orcid.org/0000-0002-4081-1583)
- Yuxia Liu (ORCID: https://orcid.org/0000-0003-1736-9253)
- Duyang Gao (ORCID: https://orcid.org/0000-0003-0605-4678)
- Zonghai Sheng (ORCID: https://orcid.org/0000-0003-0289-029X)
- Jing Ma (ORCID: https://orcid.org/0009-0006-3283-4802)
Institutions
- National University of Singapore (SG)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Shenzhen Institutes of Advanced Technology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1038/s41467-024-54167-4
- Citations
- 11
- Primary Topic
- Lanthanide and Transition Metal Complexes
- Type
- article
- Field-Weighted Citation Impact
- 1.29
Funders
- National Research Foundation
- National University of Singapore
- National Research Foundation Singapore
- National Natural Science Foundation of China
- Government of Guangdong Province
- Ministry of Education, India
- National University Health System