Cellular uptake and imaging studies of gadolinium-loaded single-walled carbon nanotubes as MRI contrast agents

We quantify here, for the first time, the intracellular uptake (J774A.1 murine macrophage cells) of gadolinium-loaded ultra-short single-walled carbon nanotubes (gadonanotubes or GNTs) in a 3 T MRI scanner using R₂ and R₂* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (ΔR₂ and ΔR2*) with increasing cell concentration. The measured ΔR₂* were about three to four times greater than the respective ΔR₂ for each cell concentration. The intracellular uptake of GNTs was validated with inductively coupled plasma optical emission spectrometry (ICP-OES), indicating an average cellular uptake of 0.44±0.09pg Gd per cell or 1.69×10⁹ Gd³⁺ ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations ≤28μM Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R₂* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T.