Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers

TLDR

Carbon nanotubes are being developed for drug and gene delivery, yet their in vivo behavior and limitations remain largely unexplored. The study functionalized water‑soluble single‑walled CNT with DTPA and labeled them with In‑111 to enable imaging of their biodistribution. The functionalized CNT were injected intravenously and tracked by gamma scintigraphy of the In‑111 label. The radiolabeled CNT were rapidly cleared from blood (half‑life ~3 h) via renal excretion, showed no accumulation in liver or spleen, and were excreted intact, indicating limited reticuloendothelial uptake and rapid clearance.

Abstract

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, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ( 111 In) 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.