title: Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction.
abstract: OBJECTIVE
  The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts.
  
  
  BACKGROUND
  Collagen deposition and interstitial fibrosis contribute to cardiac remodeling and heart failure after myocardial infarction (MI). Evaluation of myofibroblastic proliferation should provide indirect evidence of the extent of fibrosis.
  
  
  METHODS
  Of 46 Swiss-Webster mice, MI was induced in 41 by coronary artery occlusion, and 5 were unmanipulated. Of the 41 mice, 6, 6, and 5 received intravenous technetium-99m labeled CRIP for micro-single-photon emission computed tomography imaging 2, 4, and 12 weeks after MI, respectively; 8 received captopril or captopril with losartan up to 4 weeks after MI. Scrambled CRIP was used 4 weeks after MI in 6 mice; the remaining 10 of 46 mice received unradiolabeled CRIP for histologic characterization.
  
  
  RESULTS
  Maximum CRIP uptake was observed in the infarct area; quantitative uptake (percent injected dose/g) was highest at 2 weeks (2.75 +/- 0.46%), followed by 4 (2.26 +/- 0.09%) and 12 (1.74 +/- 0.24%) weeks compared with that in unmanipulated mice (0.59 +/- 0.19%). Uptake was higher at 12 weeks in the remote areas. CRIP uptake was histologically traced to myofibroblasts. Captopril alone (1.78 +/- 0.31%) and with losartan (1.13 +/- 0.28%) significantly reduced tracer uptake; scrambled CRIP uptake in infarct area (0.74 +/- 0.17%) was similar to CRIP uptake in normal myocardium.
  
  
  CONCLUSIONS
  Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling, and is responsive to antiangiotensin treatment. If proven clinically feasible, such a strategy would help identify post-MI patients likely to develop heart failure.
authors.affiliation: University of California, Irvine School of Medicine, Irvine, California, USA.
authors.forename: Susanne W M
authors.initials: SW
authors.lastname: van den Borne
authors.forename: Satoshi
authors.initials: S
authors.lastname: Isobe
authors.forename: Johan W
authors.initials: JW
authors.lastname: Verjans
authors.forename: Artiom
authors.initials: A
authors.lastname: Petrov
authors.forename: Dagfinn
authors.initials: D
authors.lastname: Lovhaug
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: H Reinier
authors.initials: HR
authors.lastname: Zandbergen
authors.forename: Youping
authors.initials: Y
authors.lastname: Ni
authors.forename: Peter
authors.initials: P
authors.lastname: Frederik
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Bente
authors.initials: B
authors.lastname: Arbo
authors.forename: Astri
authors.initials: A
authors.lastname: Rogstad
authors.forename: Alan
authors.initials: A
authors.lastname: Cuthbertson
authors.forename: Salah
authors.initials: S
authors.lastname: Chettibi
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.forename: W Matthijs
authors.initials: WM
authors.lastname: Blankesteijn
authors.forename: Jos F M
authors.initials: JF
authors.lastname: Smits
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Mani A
authors.initials: MA
authors.lastname: Vannan
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Leonard
authors.initials: L
authors.lastname: Hofstra
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
mesh_terms: D000818:Animals; D002232:Carbocyanines; D003094:Collagen / Q000378:metabolism; D003324:Coronary Artery Disease; D004719:Endomyocardial Fibrosis / Q000150:complications* / Q000000981:diagnostic imaging; D005240:Feasibility Studies; D005347:Fibroblasts; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology*; D016023:Integrins; D008297:Male; D051379:Mice; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D019275:Radiopharmaceuticals; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D020257:Ventricular Remodeling
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D016023:Integrins; D019275:Radiopharmaceuticals; D003094:Collagen