MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles.
OBJECTIVE
Targeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.


METHODS
Enzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.


RESULTS
The tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.


CONCLUSIONS
Coupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.
King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia.
Achraf
A
Al Faraj
King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia.
Asma Sultana
AS
Shaik
King Saud University, Prince Naif Center for Immunology Research, Asthma Research Chair, College of Medicine, Riyadh, Saudi Arabia.
Sibtain
S
Afzal
King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia.
Baraa
B
Al Sayed
King Saud University, Prince Naif Center for Immunology Research, Asthma Research Chair, College of Medicine, Riyadh, Saudi Arabia.
Rabih
R
Halwani
D000818:Animals; D000906:Antibodies / Q000276:immunology; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D005260:Female; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000906:Antibodies; D003287:Contrast Media; D003911:Dextrans; D008070:Lipopolysaccharides; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
MRI; iron oxide nanoparticles; lipopolysaccharide; lung imaging; lung inflammation; macrophage tracking; magnetic resonance imaging