Single-point mutated lanmodulin as a high-performance MRI contrast agent for vascular and kidney imaging.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Contrast Media* ; Kidney*/metabolism ; Kidney*/diagnostic imaging ; Magnetic Resonance Imaging*/methods ; Gadolinium*/chemistry; Animals ; Male ; Mice ; Humans ; Point Mutation ; Brain/diagnostic imaging ; Brain/metabolism ; Metalloproteins
    • Abstract:
      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 3+ 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.
      Competing Interests: Competing interests X.L., Y.L., and Z.L. are co-inventors on a Singapore patent application related to the use of lanmodulin-derived contrast agents for magnetic resonance imaging (application no. 10202400550P), filed by the National University of Singapore. The other authors declare no competing interests.
      (© 2024. The Author(s).)
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    • Grant Information:
      NRF-NRFI052019-0003 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); 2023A1515010747 Government of Guangdong Province
    • Accession Number:
      0 (Contrast Media)
      AU0V1LM3JT (Gadolinium)
      0 (lanmodulin)
      0 (Metalloproteins)
    • Publication Date:
      Date Created: 20241113 Date Completed: 20241113 Latest Revision: 20241116
    • Publication Date:
      20241116
    • Accession Number:
      PMC11561317
    • Accession Number:
      10.1038/s41467-024-54167-4
    • Accession Number:
      39537629