Kinetics of Lung Macrophages Monitored in Vivo Following Particulate Challenge in Rabbits

• Published in: Toxicology and applied pharmacology Vol. 183; no. 1; pp. 46 - 54
• Main Authors: Jones, Hazel A., Valind, Sven O., Clark, Ian C., Bolden, Geraldine E., Krausz, Thomas, Schofield, John B., Boobis, Alan R., Haslett, Christopher
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.08.2002; Elsevier
• Subjects: Animals; Antineoplastic Agents - blood; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacokinetics; Autoradiography; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; fibrosis; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); Isoquinolines - blood; Isoquinolines - metabolism; Isoquinolines - pharmacokinetics; macrophages; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Medical sciences; positron emission tomography; Rabbits; silica; Silicon Dioxide - toxicity; Toxicology; macrophages; fibrosis; positron emission tomography; silica; Lung disease; Respiratory disease; Lung; Rabbit; Intrapulmonary administration; Amorphous state; Lagomorpha; Silica; Inorganic compound; Crystalline state; Suspended particle; Vertebrata; Mammalia; Animal; Fibrosis; Non invasive method; Positron emission tomography; Macrophage
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.2002.9462

The ligand PK11195 binds specifically in macrophages. We have assessed the use of positron emission tomography (PET) of [ 11C]R-PK11195 to monitor macrophage disposition following particulate challenge to the lung. Repeated PET scanning was performed over 4 weeks following iv [ 11C]R-PK11195 in rabbits treated with 5-μm 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, 11C 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. 11C 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 [ 11C]PK11195 provides a new noninvasive approach for the study of macrophage kinetics in the lung.