title: Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: relationship to myocardial dysfunction.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined.
  
  
  RESULTS
  MI was surgically induced in pigs (n = 23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer ((99m)Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n = 5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial (99m)Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo (99m)Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y = 31.34e(0.48x), P = 0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional (99m)Tc-RP805 uptake and ex vivo MMP-2 activity.
  
  
  CONCLUSIONS
  A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased (99m)Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The (99m)Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling.
authors.affiliation: Experimental Nuclear Cardiology Laboratory, Yale University School of Medicine, New Haven, CT 06520-8017, USA.
authors.forename: Zakir H
authors.initials: ZH
authors.lastname: Sahul
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: James
authors.initials: J
authors.lastname: Song
authors.forename: Jarod
authors.initials: J
authors.lastname: McAteer
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Donald P
authors.initials: DP
authors.lastname: Dione
authors.forename: Lawrence
authors.initials: L
authors.lastname: Staib
authors.forename: Xenophon
authors.initials: X
authors.lastname: Papademetris
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Dobrucki
authors.forename: James S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
mesh_terms: D000818:Animals; D007091:Image Processing, Computer-Assisted; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000201:enzymology*; D013552:Swine; D013794:Thallium Radioisotopes; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D013794:Thallium Radioisotopes; D020782:Matrix Metalloproteinases