Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging

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.