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J Nucl Med. 2017 Jan;58(1):138-143. doi: 10.2967/jnumed.116.176198. Epub 2016 Jul 28.

Matrix Metalloproteinase-Targeted Imaging of Lung Inflammation and Remodeling.

Author information

1
Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.
2
VA Connecticut Healthcare System, West Haven, Connecticut.
3
Brown University, Providence, Rhode Island; and.
4
Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
5
Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut mehran.sadeghi@yale.edu.

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).

CONCLUSION:

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.

KEYWORDS:

SPECT; chronic obstructive pulmonary disease; interleukin-13; matrix metalloproteinases; molecular imaging

PMID:
27469361
PMCID:
PMC5209638
DOI:
10.2967/jnumed.116.176198
[Indexed for MEDLINE]
Free PMC Article

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