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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)680-687
Number of pages8
JournalMolecular Imaging and Biology
Volume17
Issue number5
DOIs
Publication statusPublished - Oct-2015

Keywords

  • 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

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