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 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. Magnetic resonance imaging (MRI) contrast agents are essential for modern medical imaging, but existing MRI contrast agents have limitations that result in poor resolution and ineffective long-term monitoring. Here, the authors report the development of a T1-MRI contrast agent based on a variant of lanmodulin, LanND-Gd, with efficient renal clearance, high relaxivity, and prolonged renal retention compared with commercially available contrast agents.