Tissue Biodistribution and Blood Clearance Rates of Intravenously Administered Carbon Nanotube Radiotracers

Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In thi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (9), p.3357-3362
Main Authors: Singh, Ravi, Pantarotto, Davide, Lacerda, Lara, Pastorin, Giorgia, Klumpp, Cédric, Prato, Maurizio, Bianco, Alberto, Kostarelos, Kostas
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Biomedical materials
Blood
Carbon
Carbon nanotubes
Dosage
Female
Fullerenes
Half lives
Half-Life
Indium
Indium Radioisotopes
Injections, Intravenous
Kidneys
Liver
Medical imaging
Medical research
Mice
Mice, Inbred BALB C
Microscopy, Electron, Transmission
Molecular Structure
Nanotubes
Nanotubes, Carbon - analysis
Pentetic Acid
Pharmacology
Physical Sciences
Tissue Distribution
Urine
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Summary:Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, singlewalled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ($^{111}ln$) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0509009103