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

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TitleIn vivo imaging of 64Cu-labeled polymer nanoparticles targeted to the lung endothelium.
Publication TypeJournal Article
Year of Publication2008
AuthorsRossin, R, Muro, S, Welch, MJ, Muzykantov, VR, Schuster, DP
JournalJ Nucl Med
Volume49
Issue1
Pagination103-11
Date Published2008 Jan
ISSN0161-5505
KeywordsAnimals, Antibodies, Monoclonal, Copper Radioisotopes, Drug Carriers, Endothelium, Heterocyclic Compounds, 1-Ring, Immunoglobulin G, Intercellular Adhesion Molecule-1, Lung, Male, Mice, Mice, Inbred C57BL, Nanoparticles, Polymers, Positron-Emission Tomography, Radiopharmaceuticals, Succinimides, Tissue Distribution
Abstract

UNLABELLED: Nanoparticles (NPs) targeting the intercellular adhesion molecule 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 (64)Cu and PET to noninvasively image the lung uptake and distribution of NPs coated with an anti-ICAM antibody.

METHODS: Model fluorescent NPs were coated with a mixture of an anti-ICAM antibody (or nonspecific IgG) and (64)Cu-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 pretreated with lipopolysaccharides (LPSs). Metabolism studies were also performed to evaluate the stability of (64)Cu-labeled NPs in lungs in vivo.

RESULTS: The lungs of mice administered anti-ICAM NPs labeled with (64)Cu were clearly imaged by small-animal PET 1, 4, and 24 h after administration. Both biodistribution and small-animal imaging showed a 3- to 4-fold higher uptake in the lungs of mice injected with ICAM-targeted NPs relative to that of the control group. Lung uptake was further enhanced by pretreating the mice with LPS, presumably because of ICAM-1 upregulation. However, an approximately 2-fold decrease in lung signal was observed in each experimental group over 24 h. Metabolism studies in lung tissues harvested from mice injected with (64)Cu-labeled anti-ICAM NPs showed considerable release of a small (64)Cu-radiometabolite from the NPs beginning as early as 1 h after injection. A decrease in lung fluorescence was also observed, most likely reflecting partial release of NPs from the lungs in vivo.

CONCLUSION: The use of small-animal PET to track (64)Cu-labeled nanostructures in vivo shows potential as a strategy for the preclinical screening of new NP drug delivery agents targeting the lung endothelium and other tissues. Future design optimization to prolong the stability of the radiolabel in vivo will further improve this promising approach.

DOI10.2967/jnumed.107.045302
Alternate JournalJ. Nucl. Med.
PubMed ID18077519
Grant ListCA86307 / CA / NCI NIH HHS / United States
HL078785 / HL / NHLBI NIH HHS / United States
HL080729 / HL / NHLBI NIH HHS / United States
HL73940 / HL / NHLBI NIH HHS / United States
P30 DK47757 / DK / NIDDK NIH HHS / United States
R01 HL71175 / HL / NHLBI NIH HHS / United States