Gadopiclenol: A q = 2 Gadolinium-Based MRI Contrast Agent Combining High Stability and Efficacy

Area of Science:

• Radiology and Medical Imaging
• Inorganic Chemistry
• Pharmacology

Background:

• Gadolinium-based contrast agents (GBCAs) are crucial for medical imaging.
• Optimizing GBCA stability and relaxivity is an ongoing area of research.
• Gadopiclenol represents a novel q=2 pyclen GBCA with potential advantages.

Purpose of the Study:

• To evaluate the in vitro and in vivo stability of gadopiclenol under stressed conditions.
• To compare the relaxivity and stability of gadopiclenol with conventional GBCAs.
• To confirm the long-term in vivo stability of gadopiclenol in rat kidneys.

Main Methods:

• Characterization of gadopiclenol and its precursor (Pi828-Gd) compared to q=1 Gd complexes.
• Determination of hydration number (q) and water residence time (τM) using luminescence and 17O NMR.
• Assessment of proton relaxivity under varying pH, temperature, and ionic conditions.
• Evaluation of kinetic inertness in human serum, acidic media, and under metal/ligand competition.
• In vivo stability assessment in rat kidneys following repeated injections.

Main Results:

• Gadopiclenol confirmed to have 2 inner-sphere water molecules (q=2), maintaining high relaxivity under physiological and stressed conditions.
• Demonstrated superior kinetic inertness compared to q=1 macrocyclic GBCAs, with minimal Gd release (<0.1 μM after 12 days in serum).
• Confirmed long-term in vivo stability in rat kidneys up to 12 months post-repeated injections.

Conclusions:

• Gadopiclenol's optimized structural design results in a highly stable and effective macrocyclic q=2 GBCA.
• Its robust stability and high relaxivity support its efficacy in diverse clinical scenarios.
• Gadopiclenol presents a promising advancement in GBCA technology for enhanced diagnostic imaging.