Open AccessNovel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging
Author(s) -
Jakub Toczek,
Thomas Bordenave,
Kiran Gona,
Hye-Yeong Kim,
Fabrice Beau,
Dimitris Georgiadis,
Isabelle Correia,
Yunpeng Ye,
Mahmoud Razavian,
Jaejoon Jung,
Olivier Lequin,
Vincent Dive,
Mehran M. Sadeghi,
Laurent Devel
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.9b01186
Subject(s) - chemistry , matrix metalloproteinase , biodistribution , in vivo , metalloproteinase , matrix metalloproteinase inhibitor , downregulation and upregulation , in vitro , abdominal aortic aneurysm , aorta , ligand (biochemistry) , pharmacology , biochemistry , gene , receptor , medicine , aneurysm , biology , radiology , microbiology and biotechnology
Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel 99m Tc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their 99g Tc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with 99m Tc 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, [ 99m Tc]- 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 [ 99m Tc]- 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 [ 99m Tc]- 1 for imaging AAA and other MMP-12-associated diseases.