@article{03d58d5f589f455fb42bbf581f58cf47,
title = "Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques",
abstract = "Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice.",
author = "Nazanin Hakimzadeh and Pinas, {Victorine A.} and Ger Molenaar and {De Waard}, Vivian and Esther Lutgens and {Van Eck-Smit}, {Berthe L.F.} and {De Bruin}, Kora and Piek, {Jan J.} and Eersels, {Jos L.H.} and Jan Booij and Verberne, {Hein J.} and Windhorst, {Albert D.}",
note = "Funding Information: This work was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project EMINENCE (grant 01C-204) and the EU FP7 project INMIND, grant nr HEALTH-F2-2011-278850 (Molenaar, Windhorst). The financial contribution of the Dutch Heart foundation is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project EMINENCE (grant 01C-204) and the EU FP7 project INMIND, grant nr HEALTH-F2-2011-278850 (Molenaar, Windhorst). The financial contribution of the Dutch Heart foundation is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2017 Hakimzadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2017",
month = nov,
doi = "10.1371/journal.pone.0187767",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",
}