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Imaging of Dysfunctional Elastogenesis in Atherosclerosis Using an Improved Gadolinium-Based Tetrameric MRI Probe Targeted to Tropoelastin

Abstract : Dysfunctional elastin turnover plays a major role in the progression of atherosclerotic plaques. Failure of tropoelastin cross-linking into mature elastin leads to the accumulation of tropoelastin within the growing plaque, increasing its instability. Here we present Gd4-TESMA, an MRI contrast agent specifically designed for molecular imaging of tropoelastin within plaques. Gd4-TESMA is a tetrameric probe composed of a tropoelastin-binding peptide (the VVGS-peptide) conjugated with four Gd(III)-DOTA-monoamide chelates. It shows a relaxivity per molecule of 34.0 ± 0.8 mM-1 s-1 (20 MHz, 298 K, pH 7.2), a good binding affinity to tropoelastin (KD = 41 ± 12 μM), and a serum half-life longer than 2 h. Gd4-TESMA accumulates specifically in atherosclerotic plaques in the ApoE-/- murine model of plaque progression, with 2 h persistence of contrast enhancement. As compared to the monomeric counterpart (Gd-TESMA), the tetrameric Gd4-TESMA probe shows a clear advantage regarding both sensitivity and imaging time window, allowing for a better characterization of atherosclerotic plaques.
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https://hal.archives-ouvertes.fr/hal-03433450
Contributor : Sara Martins Vasco de Lacerda Connect in order to contact the contributor
Submitted on : Thursday, November 18, 2021 - 5:27:49 PM
Last modification on : Friday, January 7, 2022 - 9:34:03 AM

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Federico Capuana, Alkystis Phinikaridou, Rachele Stefania, Sergio Padovan, Begoña Lavin, et al.. Imaging of Dysfunctional Elastogenesis in Atherosclerosis Using an Improved Gadolinium-Based Tetrameric MRI Probe Targeted to Tropoelastin. Journal of Medicinal Chemistry, American Chemical Society, 2021, 64 (20), pp.15250-15261. ⟨10.1021/acs.jmedchem.1c01286⟩. ⟨hal-03433450⟩

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