title: Matrix Metalloproteinase-Targeted Imaging of Lung Inflammation and Remodeling.
abstract: Imaging techniques for detection of molecular and cellular processes that precede or accompany lung diseases are needed. Matrix metalloproteinases (MMPs) play key roles in the development of pulmonary pathology. The objective of this study was to investigate the feasibility of in vivo MMP-targeted molecular imaging for detection of lung inflammation and remodeling.
  
  
  METHODS
  Lung-specific IL-13 transgenic (Club cell 10-kDa protein [CC10]-IL-13 Tg) mice and wild-type littermates were used in this study. Lung structure, gene expression, and MMP activity were assessed by histology, real-time reverse transcription polymerase chain reaction, Western blotting, and zymography. MMP activation was imaged by in vivo small-animal SPECT/CT followed by ex vivo planar imaging. Signal specificity was addressed using a control tracer. The correlation between in vivo MMP signal and gene expression was addressed.
  
  
  RESULTS
  CC10-IL-13 Tg mice developed considerable pulmonary tissue remodeling and inflammation. CD68, MMP-12, and MMP-13 were significantly higher in CC10-IL-13 Tg lungs. On in vivo small-animal SPECT/CT and ex vivo planar images, the MMP signal was significantly higher in the lungs of CC10-IL-13 Tg mice than wild-type animals. Furthermore, a nonbinding analog tracer showed significantly lower accumulation in CC10-IL-13 Tg lungs relative to the specific tracer. There was a significant correlation between small-animal SPECT/CT-derived MMP signal and CD68 expression in the lungs (r = 0.70, P < 0.01).
  
  
  CONCLUSIONS
  Small-animal SPECT/CT-based MMP-targeted imaging of the lungs is feasible and reflects pulmonary inflammation. If validated in humans, molecular imaging of inflammation and remodeling can potentially help early diagnosis and monitoring of the effects of therapeutic interventions in pulmonary diseases.
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Reza
authors.initials: R
authors.lastname: Golestani
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Razavian
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Jung
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Jakub
authors.initials: J
authors.lastname: Toczek
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Kiran
authors.initials: K
authors.lastname: Gona
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Hye-Yeong
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Brown University, Providence, Rhode Island; and.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.affiliation: Brown University, Providence, Rhode Island; and.
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: VA Connecticut Healthcare System, West Haven, Connecticut.|Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.affiliation: Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut mehran.sadeghi@yale.edu.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Mehran M
authors.initials: MM
authors.lastname: Sadeghi
mesh_terms: D056151:Airway Remodeling / Q000276:immunology*; D000818:Animals; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D011014:Pneumonia / Q000000981:diagnostic imaging / Q000276:immunology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*
chemical_list: D020782:Matrix Metalloproteinases
keywords: SPECT; chronic obstructive pulmonary disease; interleukin-13; matrix metalloproteinases; molecular imaging