vivo imaging of 64Cu-labeled polymer nanoparticles targeted to the lung endothelium

Nanoparticles (NPs) targeting the intercellular adhesionmolecule 1 (ICAM-1) hold promise as a mean of delivering therapeutics to the pulmonary endothelium in patients with acute and chronic respiratory diseases. As these new materials become available, strategies are needed to understand their behavior in vivo. We have evaluated the use of 64Cu and PET to noninvasively image the lung uptake and distribution of NPs coatedwith an anti-ICAM antibody. Methods: Model fluorescent NPs were coated with a mixture of an anti-ICAM antibody (or nonspecific IgG) and 64Cu-DOTA-IgG (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Biodistribution and small-animal PET and CT studies were performed in healthy mice and in mice pre-treated with lipopolysaccharides (LPSs). Metabolism studies were alsoperformed to evaluate the stability of 64Cu-labeledNPs in lungs in vivo.Results: The lungs of mice administered anti-ICAMNPs la