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

被引:5
作者
Matusiak, Nathalie [1 ]
van Waarde, Aren [1 ]
Rozeveld, Dennie [2 ]
van Oosterhout, Antoon J. M. [2 ]
Heijink, Irene H. [2 ]
Castelli, Riccardo [3 ]
Overkleeft, Herman S. [3 ]
Bischoff, Rainer [4 ]
Dierckx, Rudi A. J. O. [1 ]
Elsinga, Philip H. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, NL-9713 EZ Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Lab Allergy & Pulm Dis, NL-9713 EZ Groningen, Netherlands
[3] Leiden Univ, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands
[4] Univ Groningen, Groningen Res Inst Pharm, Dept Analyt Biochem, NL-9713 EZ Groningen, Netherlands
关键词
COPD; MicroPET; Lung imaging; MMP/ADAM inhibitor; BALF; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; MACROPHAGE ELASTASE; LUNG INFLAMMATION; ASTHMA; MICE; EMPHYSEMA; SPUTUM;
D O I
10.1007/s11307-015-0847-3
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Matrix metalloproteinases (MMPs) are the main proteolytic enzymes involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). A radiolabeled MMP inhibitor, [F-18]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 [F-18]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 [F-18]FB-ML5.
引用
收藏
页码:680 / 687
页数:8
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