title: 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.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 EZ, Groningen, The Netherlands. nathaliematusiak@yahoo.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Matusiak
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 EZ, Groningen, The Netherlands.
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
authors.affiliation: Laboratory of Allergy and Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dennie
authors.initials: D
authors.lastname: Rozeveld
authors.affiliation: Laboratory of Allergy and Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
authors.affiliation: Laboratory of Allergy and Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Irene H
authors.initials: IH
authors.lastname: Heijink
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Castelli
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 EZ, Groningen, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 EZ, Groningen, The Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012906:Smoke
keywords: BALF; COPD; Lung imaging; MMP/ADAM inhibitor; MicroPET
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