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

• Published in: Molecular imaging and biology Vol. 17; no. 5; pp. 680 - 687
• Main Authors: Matusiak, Nathalie, van Waarde, Aren, Rozeveld, Dennie, van Oosterhout, Antoon J. M., Heijink, Irene H., Castelli, Riccardo, Overkleeft, Herman S., Bischoff, Rainer, Dierckx, Rudi A. J. O, Elsinga, Philip H.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2015; Springer Nature B.V
• Subjects: Animals; Disease Models, Animal; Imaging; Male; Matrix Metalloproteinase Inhibitors - chemistry; Matrix Metalloproteinase Inhibitors - pharmacokinetics; Medicine; Medicine & Public Health; Mice, Inbred BALB C; Nicotiana - adverse effects; Pneumonia - chemically induced; Pneumonia - metabolism; Pneumonia - pathology; Positron-Emission Tomography - methods; Pulmonary Disease, Chronic Obstructive; Radiology; Research Article; Smoke - adverse effects; MicroPET; MMP/ADAM inhibitor; BALF; COPD; Lung imaging
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-015-0847-3

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-SUV mean ) 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.