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

Area of Science:

• Biochemistry
• Biomaterials Science
• Medical Imaging

Background:

• Magnetic resonance imaging (MRI) contrast agents improve diagnostic accuracy.
• Current agents face limitations: short imaging windows, low specificity, toxicity, and suboptimal enhancement.
• These limitations impact image resolution and long-term patient monitoring.

Purpose of the Study:

• To develop a novel protein-based MRI contrast agent with improved performance and safety.
• To engineer a lanmodulin-based agent with enhanced gadolinium binding capacity.
• To evaluate the efficacy and safety of the engineered agent (LanND-Gd) in preclinical models.

Main Methods:

• Engineered lanmodulin protein with a single-point mutation (N108D) for maximum gadolinium (Gd3+) binding.
• Loaded engineered protein with Gd3+ ions to create the LanND-Gd complex.
• Evaluated LanND-Gd in male mice for renal clearance, relaxivity, retention, and imaging performance (whole-body, brain vasculature).
• Assessed LanND-Gd in male ischemia mouse models for kidney dysfunction monitoring and toxicity.

Main Results:

• LanND-Gd demonstrated efficient renal clearance and prolonged renal retention compared to commercial agents.
• Achieved high relaxivity, enabling high-performance visualization of structures and vasculature at sub-100 micrometer resolution.
• Improved monitoring of kidney dysfunction in ischemia models.
• Minimized risks of neural toxicity and immunogenic reactions.

Conclusions:

• LanND-Gd represents a superior protein-based MRI contrast agent.
• Offers enhanced image quality, improved biocompatibility, and extended imaging capabilities.
• Shows significant potential for advancing MRI diagnostics and improving patient outcomes.