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- Title
MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [(18)F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation.
- Authors
Matusiak, Nathalie; Waarde, Aren; Rozeveld, Dennie; Oosterhout, Antoon; Heijink, Irene; Castelli, Riccardo; Overkleeft, Herman; Bischoff, Rainer; Dierckx, Rudi; Elsinga, Philip; van Waarde, Aren; van Oosterhout, Antoon J M; Heijink, Irene H; Overkleeft, Herman S; Dierckx, Rudi A J O; Elsinga, Philip H
- Abstract
Matrix metalloproteinases (MMPs) are the main proteolytic enzymes involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). A radiolabeled MMP inhibitor, [(18)F]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 [(18)F]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 [(18)F]FB-ML5.
- Subjects
POSITRON emission tomography; OBSTRUCTIVE lung disease diagnosis; DIAGNOSTIC imaging; RADIONUCLIDE imaging; MATRIX metalloproteinases; ANIMAL experimentation; BIOLOGICAL models; OBSTRUCTIVE lung diseases; MICE; PNEUMONIA; SMOKE; TOBACCO; PROTEASE inhibitors
- Publication
Molecular Imaging & Biology, 2015, Vol 17, Issue 5, p680
- ISSN
1536-1632
- Publication type
Academic Journal
- DOI
10.1007/s11307-015-0847-3