Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo.
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 gamma-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.


CONCLUSIONS
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.
Razavian
Mahmoud
M
Cardiovascular Molecular Imaging Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA.
Zhang
Jiasheng
J
Nie
Lei
L
Tavakoli
Sina
S
Razavian
Niema
N
Dobrucki
Lawrence W
LW
Sinusas
Albert J
AJ
Edwards
D Scott
DS
Azure
Michael
M
Sadeghi
Mehran M
MM
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001164:Arteriovenous Fistula / Q000000981:diagnostic imaging* / Q000201:enzymology*; D001345:Autoradiography; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002384:Catalysis; D018450:Disease Progression; D004789:Enzyme Activation; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019275:Radiopharmaceuticals; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
D001057:Apolipoproteins E; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D020782:Matrix Metalloproteinases