TY - JOUR
TI - Optical imaging of MMP-12 active form in inflammation and aneurysm
AU - Razavian, M.
AU - Bordenave, T.
AU - Georgiadis, D.
AU - Beau, F.
AU - Zhang, J.
AU - Golestani, R.
AU - Toczek, J.
AU - Jung, J.-J.
AU - Ye, Y.
AU - Kim, H.-Y.
AU - Han, J.
AU - Dive, V.
AU - Devel, L.
AU - Sadeghi, M.M.
JO - Scientific Reports
PY - 2016
VL - 6
TODO - null
SP - null
PB - Nature Publishing Group
SN - 2045-2322
TODO - 10.1038/srep38345
TODO - differentiation antigen;  fluorescent dye;  macrophage elastase;  matrix metalloproteinase inhibitor;  MMP12 protein, human;  monocyte-macrophage differentiation antigen;  peptide;  protein binding;  quaternary ammonium derivative;  RXP470.1 peptide;  sulfonic acid derivative;  ZW800-1 compound, aneurysm;  animal;  C57BL mouse;  carotid artery;  chemistry;  diagnostic imaging;  disease model;  fluorescence imaging;  gene expression;  genetics;  human;  immunology;  inflammation;  macrophage;  metabolism;  mouse;  pathology;  procedures;  synthesis, Aneurysm;  Animals;  Antigens, Differentiation;  Carotid Arteries;  Disease Models, Animal;  Fluorescent Dyes;  Gene Expression;  Humans;  Inflammation;  Macrophages;  Matrix Metalloproteinase 12;  Matrix Metalloproteinase Inhibitors;  Mice;  Mice, Inbred C57BL;  Optical Imaging;  Peptides;  Protein Binding;  Quaternary Ammonium Compounds;  Sulfonic Acids
TODO - Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications.
ER -