title: Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo.
abstract: 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.
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Razavian
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.forename: Sina
authors.initials: S
authors.lastname: Tavakoli
authors.forename: Niema
authors.initials: N
authors.lastname: Razavian
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Dobrucki
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
authors.forename: D Scott
authors.initials: DS
authors.lastname: Edwards
authors.forename: Michael
authors.initials: M
authors.lastname: Azure
authors.forename: Mehran M
authors.initials: MM
authors.lastname: Sadeghi
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D020782:Matrix Metalloproteinases