RT Journal Article
SR Electronic
T1 Molecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1107
OP 1115
DO 10.2967/jnumed.110.075259
VO 51
IS 7
A1 Razavian, Mahmoud
A1 Zhang, Jiasheng
A1 Nie, Lei
A1 Tavakoli, Sina
A1 Razavian, Niema
A1 Dobrucki, Lawrence W.
A1 Sinusas, Albert J.
A1 Edwards, D. Scott
A1 Azure, Michael
A1 Sadeghi, Mehran M.
YR 2010
UL http://jnm.snmjournals.org/content/51/7/1107.abstract
AB Rupture and dissection are major causes of morbidity and mortality in arterial aneurysm and occur more frequently in rapidly expanding aneurysms. Current imaging modalities provide little information on aneurysm beyond size. Matrix metalloproteinase (MMP) activation plays a key role in the pathogenesis of aneurysm. We investigated whether imaging MMP activation in aneurysm helps predict its propensity to expansion. Methods: We used a model of carotid aneurysm in apolipoprotein E–deficient (apoE−/−) mice. Radiotracers with specificity for activated MMPs were used to detect and quantify MMP activation by micro-SPECT/CT in vivo. Tracer uptake was confirmed by autoradiography and γ-well counting, and specificity was demonstrated using an excess of unlabeled precursor and a specific MMP inhibitor. Results: We demonstrated that several MMPs are expressed with distinct temporal patterns in aneurysm. Significant focal uptake was observed in aneurysmal carotid arteries, peaking at 4 wk after aneurysm induction. In a group of animals imaged serially at 2 and 4 wk after aneurysm induction, MMP tracer uptake at 2 wk correlated well with the vessel area assessed by histology at 4 wk. Conclusion: Molecular imaging of MMP activation is a useful experimental, and potentially clinical, tool to noninvasively predict the propensity of an aneurysm to expansion in vivo.