Positron emission tomography: a novel technique for investigating the biodistribution and transport of nanoparticles.
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, approximately 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.
Palko
Heather A
HA
Department of Chemistry, University of California-Davis, Davis, California, USA.
Fung
Jennifer Y
JY
Louie
Angelique Y
AY
D000393:Air Pollutants / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D023401:Animal Use Alternatives / Q000379:methods; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003301:Copper Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D021621:Imaging, Three-Dimensional / Q000379:methods; D017879:Isothiocyanates / Q000737:chemistry; D057230:Limit of Detection; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D011137:Polystyrenes / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D051598:Whole Body Imaging
C087160:2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid; D000393:Air Pollutants; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D052638:Particulate Matter; D011137:Polystyrenes