1. Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging.
- Author
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Toczek J, Bordenave T, Gona K, Kim HY, Beau F, Georgiadis D, Correia I, Ye Y, Razavian M, Jung JJ, Lequin O, Dive V, Sadeghi MM, and Devel L
- Subjects
- Animals, Aortic Aneurysm, Abdominal diagnostic imaging, Humans, Male, Matrix Metalloproteinase Inhibitors pharmacokinetics, Mice, Mice, Inbred C57BL, Radioactive Tracers, Radiochemistry, Tissue Distribution, Up-Regulation, Aorta diagnostic imaging, Matrix Metalloproteinase 12 metabolism, Matrix Metalloproteinase Inhibitors chemistry, Molecular Imaging methods, Organotechnetium Compounds chemistry
- Abstract
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 their99g Tc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with99m 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.- Published
- 2019
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