Towards an Improved Design of MRI Contrast Agents: Synthesis and Relaxometric Characterisation of Gd-HPDO3A Analogues.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 9513783 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3765 (Electronic) Linking ISSN: 09476539 NLM ISO Abbreviation: Chemistry Subsets: MEDLINE

Original Publication: Weinheim, Germany : Wiley-VCH

Contrast Media/*chemistry ; Gadolinium/*chemistry ; Lanthanoid Series Elements/*chemistry ; Magnetic Resonance Imaging/*methods; Europium/chemistry ; Heterocyclic Compounds/chemistry ; Kinetics ; Organometallic Compounds/chemistry ; Water

The properties of Ln ^III -HPDO3A complexes as relaxation enhancers and paraCEST agents are essentially related to the hydroxylpropyl moiety. A series of three HPDO3A derivatives, with small modifications to the hydroxyl arm, were herein investigated to understand how heightened control can be gained over the parameters involved in the design of these agents. A full ¹ H and ¹⁷ O-NMR relaxometric analysis was conducted and demonstrated that increasing the length of the OH group from the lanthanide centre significantly enhanced the water exchange rate of the gadolinium complex, but with a subsequent reduction in kinetic stability. Alternatively, the introduction of an additional methyl group, which increased the steric bulk around the OH moiety, resulted in the formation of almost exclusively the TSAP isomer (95 %) as identified by ¹ H-NMR of the europium complex. The gadolinium analogue of this complex also exhibited a very fast water exchange rate, but with no detectable loss of kinetic stability. This complex therefore demonstrates a notable improvement over Gd-HPDO3A.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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FESR 2014/2020 Bando IR 2 / 309-17 Regione Piemonte; AC15209 European Cooperation in Science and Technology

Keywords: MRI contrast agents; gadolinium; lanthanides; macrocycles; relaxometry

0 (Contrast Media)
0 (Heterocyclic Compounds)
0 (Lanthanoid Series Elements)
0 (Organometallic Compounds)
0199MV609F (gadoteridol)
059QF0KO0R (Water)
444W947O8O (Europium)
AU0V1LM3JT (Gadolinium)

Date Created: 20200306 Date Completed: 20200818 Latest Revision: 20200818

20250114

10.1002/chem.202000479

32133687