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.
MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [18F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation / Matusiak, Nathalie; van Waarde, Aren; Rozeveld, Dennie; van Oosterhout, Antoon J. M.; Heijink, Irene H.; Castelli, Riccardo; Overkleeft, Hermen S.; Bischoff, Rainer; Dierckx, Rudi A. J. O.; Elsinga, Philip H.. - In: MOLECULAR IMAGING AND BIOLOGY. - ISSN 1536-1632. - 17:5(2015), pp. 680-687. [10.1007/s11307-015-0847-3]
MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [18F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation
CASTELLI, Riccardo;
2015-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
