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Published ahead of print on December 9, 2005, doi:10.1164/rccm.200506-865OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 4, February 2006, 426-431

A more recent version of this article appeared on February 15, 2006
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Submitted on June 4, 2005
Accepted on December 2, 2005

Do Inhaled Carbon Nanoparticles Translocate Directly Into the Circulation in Man?

Nicholas L Mills1*, Nadia Amin1, Simon D Robinson1, Atul Anand1, John Davies2, Dilip Patel2, Jesus M de la Fuente3, Flemming R Cassee4, Nicholas A Boon1, William MacNee5, Alistair M Millar6, Ken Donaldson5, and David E Newby1

1 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom, 2 Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, 3 Centre for Cell Engineering, Glasgow University, Glasgow, United Kingdom, 4 National Institute for Public Health and the Environment, Bilthoven, The Netherlands, 5 ELEGI Colt Research Laboratories, University of Edinburgh, Edinburgh, United Kingdom, 6 Radiopharmacy, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom

* To whom correspondence should be addressed. E-mail: nick.mills{at}ed.ac.uk.

Rationale Increased exposure to particulate air pollution (PM10) is a risk factor for death and hospitalisation with cardiovascular disease. It has been suggested that the nanoparticulate component of PM10 is capable of translocating into the circulation with the potential for direct effects on the vasculature. Objective The study aim was to determine the extent to which inhaled Technetium-99m 99mTc) labelled carbon nanoparticles (Technegas), were able to access the systemic circulation. Methods and Main Results Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 hours. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 minutes. Thin layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound 99mTc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound 99mTc at the origin. Gamma camera images demonstrated high levels of Technegas retention (95.6 ± 1.7% at 6 hours) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. Conclusions The majority of 99mTc-labelled carbon nanoparticles remain within the lung up to six hours after inhalation. In contrast to previous published studies, thin layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.
Key words: AIR POLLUTION, NANOPARTICLES, LUNG, CIRCULATION




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