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Published on: April 13, 2010
Kinetics of lung macrophages monitored in vivo following particulate challenge in rabbits
Hazel A Jones1, Sven O Valind, Ian C Clark
1Division of Medicine, Imperial College, Hammersmith Campus, London W12 ONN, United Kingdom.
Abstract:
The ligand PK11195 binds specifically in macrophages. We have assessed the use of positron emission tomography (PET) of [(11)C]R-PK11195 to monitor macrophage disposition following particulate challenge to the lung. Repeated PET scanning was performed over 4 weeks following iv [(11)C]R-PK11195 in rabbits treated with 5-microm particles of either amorphous (aSiO(2)) or microcrystalline (xSiO(2)) silica instilled into right upper pulmonary lobes. aSiO(2) resulted in increased macrophages, few neutrophils, and no fibrosis, while xSiO(2) increased macrophages and neutrophils and caused fibrosis. After both stimuli, (11)C localized to the challenged area and correlated with macrophage numbers. Radioactive counts in challenged/control lung regions peaked at 4 days for aSiO(2) (2.88, n = 2) and 6 days for xSiO(2) (4.62, n = 2). The signal remained elevated throughout the study (aSiO(2), 2.33 +/- 0.77 SD, n = 14; xSiO(2), 3.99 +/- 1.29 SD, n = 9), as did macrophage accumulation. (11)C also localized to regions consistent with macrophage traffic through lymph ducts 6 days after aSiO(2) challenge, but not until 4 weeks after xSiO(2). Specific binding of R-PK11195 in macrophages was demonstrated by microautoradiography in lavage fluid from an inflamed rabbit knee-joint model. These data suggest that PET scanning after [(11)C]PK11195 provides a new noninvasive approach for the study of macrophage kinetics in the lung.
Insights
Positron emission tomography (PET) with [(11)C]R-PK11195 noninvasively monitors macrophage activity in the lung. This technique tracks macrophage accumulation and kinetics following silica particle exposure, offering a new research approach.
Area of Science:
- Pulmonary Medicine
- Radiology
- Immunology
Background:
- Macrophages play a critical role in lung inflammation and response to particulate matter.
- Assessing macrophage kinetics noninvasively is crucial for understanding lung disease progression.
- The ligand PK11195 specifically binds to macrophages, making it a potential imaging target.
Purpose of the Study:
- To evaluate the utility of positron emission tomography (PET) using [(11)C]R-PK11195 for monitoring macrophage disposition in the lung.
- To compare the macrophage response to amorphous (aSiO(2)) and microcrystalline (xSiO(2)) silica particles.
- To establish a noninvasive method for studying macrophage kinetics in vivo.
Main Methods:
- Rabbits received intravenous injections of [(11)C]R-PK11195 for PET scanning over four weeks.
- Lung lobes were challenged with either aSiO(2) or xSiO(2) particles.
- Macrophage accumulation and distribution were assessed using PET imaging and correlated with histological findings.
Main Results:
- [(11)C]R-PK11195 PET imaging successfully localized to silica-challenged lung regions, correlating with macrophage numbers.
- Radioactive counts peaked at 4-6 days post-challenge and remained elevated throughout the study, mirroring macrophage accumulation.
- PET imaging detected macrophage trafficking through lymph ducts, with earlier detection after aSiO(2) compared to xSiO(2).
Conclusions:
- [(11)C]R-PK11195 PET scanning provides a novel, noninvasive method for assessing macrophage kinetics in the lung.
- The technique can differentiate responses to different silica particle types, correlating with inflammatory and fibrotic outcomes.
- This approach holds promise for studying macrophage-related lung diseases and therapeutic interventions.
