Journal Article

Chiral Switch of Gadopiclenol: New Standards in MRI Probes

Bényei, Attila, Colombo Serra, Sonia, Boccalon, Mariangela, Tedoldi, Fabio, Fretta, Roberta, Buonsanti, Federica, Napolitano, Roberta, Baranyai, Zsolt, Fringuello Mingo, Alberto, Guidolin, Nicol, Giovenzana, Giovanni Battista, Demitri, Nicola, Botta, Mauro

2025

Overview

Magnetic Resonance Imaging (MRI) plays a vital role in the accurate diagnosis of numerous human diseases and disorders, with Gd(III)‐based contrast agents (GBCAs) being used in ≈30%–40% of procedures, resulting in ≈30 million doses administered annually worldwide. The careful design of a rigid macrocyclic chelator featuring a highly hydrophilic periphery leads to the development of gadopiclenol, the first bis‐hydrated Gd(III)‐based MRI contrast agent, recently approved for clinical use by both the FDA and EMA. The stereochemistry of the coordinating arms is found to play a crucial role in the remarkable thermodynamic stability and inertness of the Gd(III)‐complex with the RRR/SSS‐stereoisomer of this heptadentate chelating agent, ensuring its safety in vivo. The exceptional stability of the most effective gadopiclenol enantiomeric pair (RRR/SSS), coupled with a relaxivity 2 to 3 times higher than that of currently used GBCAs, has enabled the use of reduced doses while ensuring non‐inferior image contrast. The stereochemistry of the coordinating side arms of the polyaminocarboxylic ligand piclenol is found to be crucial in determining the MRI contrast efficiency of the corresponding Gd(III)‐complex (“gadopiclenol”). This finding allowed to identify the most effective enantiomer of gadopiclenol, the latter being used as the first clinically approved q = 2 Gd‐based contrast agent.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Animals / Chromatography / Contrast agents / Contrast Media - chemistry / coordination chemistry / diagnostics / Gadolinium - chemistry / Humans / imaging / Ligands / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Magnetic Resonance Imaging - standards / Organometallic Compounds - chemistry / physical chemistry / Single crystals / stereochemistry / Stereoisomerism / synthesis