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Inhalation Toxicology
International Forum for Respiratory Research
Volume 22, 2010 - Issue 8
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Research Article

Positron emission tomography: A novel technique for investigating the biodistribution and transport of nanoparticles

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Pages 657-688 | Received 22 May 2009, Accepted 18 Feb 2010, Published online: 07 Apr 2010
 

Abstract

Particulate matter (PM) has been associated with serious health effects within but also outside of the pulmonary system. Therefore, there is great interest in studying the biodistribution of PM after delivery to the lung to correlate sites of extrapulmonary particle accumulation and abnormal conditions known to be associated with PM exposure. Traditional PM tracking studies have introduced nanoparticles to animal models or humans and have determined the biodistribution with gamma counting, gamma camera, and inductively coupled plasma mass spectrometry (ICP-MS). The authors here demonstrate that positron emission tomography (PET) is a powerful tool that can be employed to visualize the deposition and track the fate of nanoparticles in the mouse model. In these studies, ∼100-nm polystyrene nanoparticles were labeled with the positron emitter 64Cu bound by the chelator (S)-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The labeled nanoparticles were instilled intratracheally into C57BL/6 mice; the initial deposition and biodistribution through 48 h was determined by PET imaging. In addition to static imaging, dynamic imaging was performed in the Sprague-Dawley rat model to demonstrate that PET can capture particle movement in pseudo-time-lapse videos. Particle deposition and clearance was clearly identified by PET, and the same animals could be imaged repeatedly without any adverse effects from anesthesia. PET has the potential to require many fewer animals than traditional methods while still providing quantitative results. In addition, the initial deposition pattern in each animal can be accurately determined and the same animal monitored over time so that data interpretation is not clouded by variations in initial deposition profiles.

Acknowledgements

We would like to thank the Center for Molecular and Genomic Imaging at UC Davis for their assistance with the animal imaging, and Drs. Kent Pinkerton and Dennis Wilson (University of California at Davis) for helpful discussions. Imaging work performed at the Center for Molecular and Genomic Imaging, University of California, Davis is supported in part by a NCI Small Animal Imaging Resource grant (U24 CA 110804).

Declaration of interest

This research has been funded wholly or in part by the United States Environmental Protection Agency through STAR grant RD832414 to the University of California at Davis. It has not been subjected to the Agency’s required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred.

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