MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [(18)F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation.

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.

• Authors: Nathalie Matusiak, Aren van Waarde, Dennie Rozeveld, Antoon J M van Oosterhout, Irene H Heijink, Riccardo Castelli, Herman S Overkleeft, Rainer Bischoff, Rudi A J O Dierckx, Philip H Elsinga
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 17 Issue 5 Pg. 680-7 (Oct 2015) ISSN: 1860-2002 [Electronic] United States
• PMID: 25822732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Matrix Metalloproteinase Inhibitors
• Smoke

Topics

• Animals
• Disease Models, Animal
• Male
• Matrix Metalloproteinase Inhibitors (chemistry, pharmacokinetics)
• Mice, Inbred BALB C
• Pneumonia (chemically induced, metabolism, pathology)
• Positron-Emission Tomography (methods)
• Pulmonary Disease, Chronic Obstructive
• Smoke (adverse effects)
• Nicotiana (adverse effects)