In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysacchar...

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Main Authors: Matthew J. Hardwick, Ming-Kai Chen, Kwamena Baidoo, Martin G. Pomper, Tomás R. Guilarte
Format: Article
Language:English
Published: SAGE Publishing 2005-10-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2005.05133
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author Matthew J. Hardwick
Ming-Kai Chen
Kwamena Baidoo
Martin G. Pomper
Tomás R. Guilarte
author_facet Matthew J. Hardwick
Ming-Kai Chen
Kwamena Baidoo
Martin G. Pomper
Tomás R. Guilarte
author_sort Matthew J. Hardwick
collection DOAJ
description The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [ 123 I]-( R )-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [ 11 C]-( R )-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.
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spelling doaj-art-2dbfba2cd2c14bf7b5d620faa6b831ea2025-01-03T00:11:32ZengSAGE PublishingMolecular Imaging1536-01212005-10-01410.2310/7290.2005.0513310.2310_7290.2005.05133In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of InflammationMatthew J. Hardwick0Ming-Kai Chen1Kwamena Baidoo2Martin G. Pomper3Tomás R. Guilarte4Loyola CollegeJohns Hopkins University, Bloomberg School of Public HealthJohns Hopkins University, Bloomberg School of Public HealthJohns Hopkins Hospital, Baltimore, MDJohns Hopkins University, Bloomberg School of Public HealthThe ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [ 123 I]-( R )-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [ 11 C]-( R )-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.https://doi.org/10.2310/7290.2005.05133
spellingShingle Matthew J. Hardwick
Ming-Kai Chen
Kwamena Baidoo
Martin G. Pomper
Tomás R. Guilarte
In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
Molecular Imaging
title In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
title_full In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
title_fullStr In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
title_full_unstemmed In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
title_short In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation
title_sort in vivo imaging of peripheral benzodiazepine receptors in mouse lungs a biomarker of inflammation
url https://doi.org/10.2310/7290.2005.05133
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