@article{3021164,
    title = "Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging",
    author = "Toczek, J. and Bordenave, T. and Gona, K. and Kim, H.-Y. and Beau, F. and Georgiadis, D. and Correia, I. and Ye, Y. and Razavian, M. and Jung, J.-J. and Lequin, O. and Dive, V. and Sadeghi, M.M. and Devel, L.",
    journal = "Journal of Medicinal Chemistry",
    year = "2019",
    volume = "62",
    number = "21",
    pages = "9743-9752",
    publisher = "American Chemical Society",
    issn = "0022-2623, 1520-4804",
    doi = "10.1021/acs.jmedchem.9b01186",
    keywords = "macrophage elastase;  metalloproteinase inhibitor;  technetium 99m;  macrophage elastase;  matrix metalloproteinase inhibitor;  technetium complex;  tracer, abdominal aortic aneurysm;  animal experiment;  Article;  autoradiography;  binding affinity;  carbon nuclear magnetic resonance;  controlled study;  drug binding;  drug clearance;  drug distribution;  drug stability;  drug structure;  drug synthesis;  gene expression;  heteronuclear single quantum coherence;  high performance liquid chromatography;  human;  in vitro study;  in vivo study;  isotope labeling;  molecular imaging;  mouse;  nonhuman;  plasma clearance;  proton nuclear magnetic resonance;  radiochemistry;  upregulation;  animal;  aorta;  C57BL mouse;  chemistry;  diagnostic imaging;  male;  metabolism;  molecular imaging;  procedures;  tissue distribution, Animals;  Aorta;  Aortic Aneurysm, Abdominal;  Humans;  Male;  Matrix Metalloproteinase 12;  Matrix Metalloproteinase Inhibitors;  Mice;  Mice, Inbred C57BL;  Molecular Imaging;  Organotechnetium Compounds;  Radioactive Tracers;  Radiochemistry;  Tissue Distribution;  Up-Regulation",
    abstract = "Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel 99mTc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their 99gTc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with 99mTc was shown to be efficient and stable in both buffer and mouse blood. The tracers showed major differences in their biodistribution and blood clearance. On the basis of its in vivo performance, [99mTc]-1 was selected for evaluation in murine AAA, where MMP-12 gene expression is upregulated. Autoradiography of aortae at 2 h postinjection revealed high uptake of [99mTc]-1 in AAA relative to adjacent aorta. Tracer uptake specificity was demonstrated through in vivo competition. This study paves the way for further evaluation of [99mTc]-1 for imaging AAA and other MMP-12-associated diseases. Copyright © 2019 American Chemical Society."
}