Kinetics of lung macrophages monitored in vivo following particulate challenge in rabbits

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.