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

doi:10.1007/s11307-015-0847-3

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 journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	680-687
Number of pages	8
Journal	Molecular Imaging and Biology
Volume	17
Issue number	5
DOIs	https://doi.org/10.1007/s11307-015-0847-3
Publication status	Published - 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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Matusiak, N., van Waarde, A., Rozeveld, D., van Oosterhout, A. J. M., Heijink, I. H., Castelli, R., Overkleeft, H. S., Bischoff, R., Dierckx, R. A. J. O., & Elsinga, P. H. (2015). MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [F-18]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation. Molecular Imaging and Biology, 17(5), 680-687. https://doi.org/10.1007/s11307-015-0847-3

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title = "MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [F-18]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, [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.",

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",

author = "Nathalie Matusiak and {van Waarde}, Aren and Dennie Rozeveld and {van Oosterhout}, {Antoon J. M.} and Heijink, {Irene H.} and Riccardo Castelli and Overkleeft, {Herman S.} and Rainer Bischoff and Dierckx, {Rudi A. J. O.} and Elsinga, {Philip H.}",

year = "2015",

month = oct,

doi = "10.1007/s11307-015-0847-3",

language = "English",

volume = "17",

pages = "680--687",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer",

number = "5",

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Matusiak, N, van Waarde, A, Rozeveld, D, van Oosterhout, AJM , Heijink, IH, Castelli, R, Overkleeft, HS, Bischoff, R , Dierckx, RAJO & Elsinga, PH 2015, 'MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [F-18]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation', Molecular Imaging and Biology, vol. 17, no. 5, pp. 680-687. https://doi.org/10.1007/s11307-015-0847-3

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T1 - MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [F-18]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation

AU - Matusiak, Nathalie

AU - van Waarde, Aren

AU - Rozeveld, Dennie

AU - van Oosterhout, Antoon J. M.

AU - Heijink, Irene H.

AU - Castelli, Riccardo

AU - Overkleeft, Herman S.

AU - Bischoff, Rainer

AU - Dierckx, Rudi A. J. O.

AU - Elsinga, Philip H.

PY - 2015/10

Y1 - 2015/10

N2 - 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.

AB - 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.

KW - COPD

KW - MicroPET

KW - Lung imaging

KW - MMP/ADAM inhibitor

KW - BALF

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - BRONCHOALVEOLAR LAVAGE FLUID

KW - MATRIX METALLOPROTEINASES

KW - TISSUE INHIBITOR

KW - MACROPHAGE ELASTASE

KW - LUNG INFLAMMATION

KW - ASTHMA

KW - MICE

KW - EMPHYSEMA

KW - SPUTUM

U2 - 10.1007/s11307-015-0847-3

DO - 10.1007/s11307-015-0847-3

M3 - Article

C2 - 25822732

SN - 1536-1632

VL - 17

SP - 680

EP - 687

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 5

ER -