Matrix Metalloproteinase-Targeted Imaging of Lung Inflammation and Remodeling
Reza Golestani1,2, Mahmoud Razavian1,2, Yunpeng Ye1,2
1Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.
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.
Insights
Molecular imaging using SPECT/CT can detect lung inflammation and remodeling by targeting matrix metalloproteinases (MMPs). This technique shows promise for early diagnosis and monitoring of pulmonary diseases.
Area of Science:
- Pulmonary Medicine
- Molecular Imaging
- Biomarkers
Background:
- Matrix metalloproteinases (MMPs) are crucial in lung disease development.
- Current imaging methods lack the sensitivity to detect early molecular and cellular changes in lung diseases.
Purpose of the Study:
- To assess the feasibility of in vivo MMP-targeted molecular imaging for detecting lung inflammation and remodeling.
- To correlate imaging findings with established markers of inflammation.
Main Methods:
- Utilized IL-13 transgenic mice and wild-type littermates.
- Assessed lung pathology via histology, gene expression, and MMP activity assays.
- Employed in vivo small-animal SPECT/CT and ex vivo planar imaging for MMP activation detection.
Main Results:
- Transgenic mice exhibited significant pulmonary inflammation and remodeling with elevated MMP-12 and MMP-13 levels.
- In vivo SPECT/CT demonstrated higher MMP signals in transgenic mouse lungs compared to controls.
- A significant correlation was observed between MMP signal intensity and CD68 expression, a marker of inflammation.
Conclusions:
- Small-animal SPECT/CT imaging targeting MMPs is a feasible method for visualizing lung inflammation and remodeling.
- This molecular imaging approach holds potential for early diagnosis and therapeutic monitoring in pulmonary diseases.
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