Abstract
Matrix metalloproteinases (MMPs) are the main proteolytic enzymes involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). A radiolabeled MMP inhibitor, [18F]FB-ML5, was prepared, and its in vivo kinetics were tested in a mouse model of pulmonary inflammation. BALB/c mice were exposed for 4 days to cigarette smoke (CS) or air. On the fifth day, a dynamic microPET scan was made with [18F]FB-ML5. Standardized uptake values (PET-SUVmean) were 0.19 ± 0.06 in the lungs of CS-exposed mice (n = 6) compared to 0.11 ± 0.03 (n = 5) in air-exposed controls (p < 0.05), 90 min post-injection MMP-9 levels in bronchoalveolar lavage fluid (BALF) were increased from undetectable level to 4615 ± 1963 pg/ml by CS exposure. Increased MMP expression in a COPD mouse model was shown to lead to increased retention of [18F]FB-ML5.
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Abbreviations
- ADAM:
-
A disintegrin and metalloproteinase
- BAL:
-
Bronchoalveolar lavage
- BALF:
-
Bronchoalveolar lavage fluid
- COPD:
-
Chronic obstructive pulmonary disease
- CS:
-
Cigarette smoke
- CT:
-
Computed tomography
- ECM:
-
Extracellular matrix
- ELISA:
-
Enzyme-linked immunosorbent assay
- HPLC:
-
High-performance liquid chromatography
- MMP:
-
Matrix metalloproteinase
- MMPI:
-
Matrix metalloproteinase inhibitor
- NIRF:
-
Near-infrared fluorescence
- PBS:
-
Phosphate-buffered saline
- PET:
-
Positron emission tomography
- ROIs:
-
Regions of interest
- RP:
-
Reversed-phase
- SUV:
-
Standardized uptake value
- TFA:
-
Trifluoroacetic acid
- TIMP:
-
Tissue inhibitor of matrix metalloproteinase
- UV:
-
Ultraviolet
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Acknowledgments
The authors wish to thank the Dutch Technology Foundation (STW) for financial support (project 08008). The authors would also like to thank Jurgen Sijbesma for his assistance during the scanning procedure, Uilke Brouwer for ex vivo bronchoalveolar lavage, and Renée Gras for differential cell counts.
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The authors declare that they have no conflict of interest.
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Matusiak, N., van Waarde, A., Rozeveld, D. et al. MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [18F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation. Mol Imaging Biol 17, 680–687 (2015). https://doi.org/10.1007/s11307-015-0847-3
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DOI: https://doi.org/10.1007/s11307-015-0847-3