Alkystis Phinikaridou, Giuseppe Digilio, Federico Capuana, Silvio Aime, René M. Botnar, Sergio Padovan, Eyad Almouazen, Begoña Lavin, Laurence Heinrich-Balard, Sara Lacerda, Yves Chevalier, Rachele Stefania, Department of Life Sciences and Systems Biology [University of Turin], University of Turin, School of Biomedical Engineering and Imaging Sciences, King's college London, King‘s College London, Molecular Biotechnology Center, Università degli studi di Torino (UNITO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Université d'Orléans (UO), Laboratoire d'automatique, de génie des procédés et de génie pharmaceutique (LAGEPP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Pontificia Universidad Católica de Chile: Santiago, Región Metropolitana, CL, IRCCS SDN Napoli, Università degli Studi del Piemonte Orientale, Dipartimento di Scienze e Innovazione Tecnologica, Alessandria, Italy, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Pontificia Universidad Católica de Chile (UC), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Università degli studi di Torino = University of Turin (UNITO), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), Martins Vasco de Lacerda, Sara, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
International audience; 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.