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

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0509009103

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.