Chiral Switch of Gadopiclenol: New Standards in MRI Probes

Abstract 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 ri...

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Main Authors: Roberta Napolitano, Nicol Guidolin, Mariangela Boccalon, Alberto Fringuello Mingo, Sonia Colombo Serra, Federica Buonsanti, Roberta Fretta, Nicola Demitri, Attila Bényei, Mauro Botta, Giovanni Battista Giovenzana, Fabio Tedoldi, Zsolt Baranyai
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202415321
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author Roberta Napolitano
Nicol Guidolin
Mariangela Boccalon
Alberto Fringuello Mingo
Sonia Colombo Serra
Federica Buonsanti
Roberta Fretta
Nicola Demitri
Attila Bényei
Mauro Botta
Giovanni Battista Giovenzana
Fabio Tedoldi
Zsolt Baranyai
author_facet Roberta Napolitano
Nicol Guidolin
Mariangela Boccalon
Alberto Fringuello Mingo
Sonia Colombo Serra
Federica Buonsanti
Roberta Fretta
Nicola Demitri
Attila Bényei
Mauro Botta
Giovanni Battista Giovenzana
Fabio Tedoldi
Zsolt Baranyai
author_sort Roberta Napolitano
collection DOAJ
description Abstract 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.
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institution DOAJ
issn 2198-3844
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publishDate 2025-04-01
publisher Wiley
record_format Article
series Advanced Science
spelling doaj-art-e3f548909a224407ad43cb5c7c5d20192025-08-20T03:09:08ZengWileyAdvanced Science2198-38442025-04-011214n/an/a10.1002/advs.202415321Chiral Switch of Gadopiclenol: New Standards in MRI ProbesRoberta Napolitano0Nicol Guidolin1Mariangela Boccalon2Alberto Fringuello Mingo3Sonia Colombo Serra4Federica Buonsanti5Roberta Fretta6Nicola Demitri7Attila Bényei8Mauro Botta9Giovanni Battista Giovenzana10Fabio Tedoldi11Zsolt Baranyai12Bracco Research Centre Bracco Imaging SpA Via Ribes 5 Colleretto Giacosa 10010 TO ItalyCRB Trieste Bracco Imaging SpA AREA Science Park Basovizza 34149 TS ItalyCRB Trieste Bracco Imaging SpA AREA Science Park Basovizza 34149 TS ItalyBracco Research Centre Bracco Imaging SpA Via Ribes 5 Colleretto Giacosa 10010 TO ItalyBracco Research Centre Bracco Imaging SpA Via Ribes 5 Colleretto Giacosa 10010 TO ItalyBracco Research Centre Bracco Imaging SpA Via Ribes 5 Colleretto Giacosa 10010 TO ItalyBracco Research Centre Bracco Imaging SpA Via Ribes 5 Colleretto Giacosa 10010 TO ItalyXRD2 Beamline Elettra‐Sincrotrone Trieste S.C.p.A. S.S. 14 Km 163.5 in Area Science Park Basovizza 34149 TS ItalyDepartment of Physical Chemistry University of Debrecen Egyetem tér 1 Debrecen H‐4032 HungaryDipartimento di Scienze e Innovazione Tecnologica, Piattaforma di Risonanze Magnetiche (PRISMA‐UPO) Università del Piemonte Orientale “A. Avogadro” Viale Teresa Michel 11 Alessandria 15121 ItalyDipartimento di Scienze del Farmaco (DSF) Università del Piemonte Orientale “A. Avogadro” Largo Donegani 2/3 Novara 28100 ItalyHeadquarters Bracco Imaging SpA Via Egidio Folli 50 Milano 20134 MI ItalyCRB Trieste Bracco Imaging SpA AREA Science Park Basovizza 34149 TS ItalyAbstract 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.https://doi.org/10.1002/advs.202415321coordination chemistrydiagnosticsimagingphysical chemistrystereochemistrysynthesis
spellingShingle Roberta Napolitano
Nicol Guidolin
Mariangela Boccalon
Alberto Fringuello Mingo
Sonia Colombo Serra
Federica Buonsanti
Roberta Fretta
Nicola Demitri
Attila Bényei
Mauro Botta
Giovanni Battista Giovenzana
Fabio Tedoldi
Zsolt Baranyai
Chiral Switch of Gadopiclenol: New Standards in MRI Probes
Advanced Science
coordination chemistry
diagnostics
imaging
physical chemistry
stereochemistry
synthesis
title Chiral Switch of Gadopiclenol: New Standards in MRI Probes
title_full Chiral Switch of Gadopiclenol: New Standards in MRI Probes
title_fullStr Chiral Switch of Gadopiclenol: New Standards in MRI Probes
title_full_unstemmed Chiral Switch of Gadopiclenol: New Standards in MRI Probes
title_short Chiral Switch of Gadopiclenol: New Standards in MRI Probes
title_sort chiral switch of gadopiclenol new standards in mri probes
topic coordination chemistry
diagnostics
imaging
physical chemistry
stereochemistry
synthesis
url https://doi.org/10.1002/advs.202415321
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