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 R-2 and R-2* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (Delta R-2 and Delta R-2*) with increasing cell concentration. The measured Delta R-2* were about three to four times greater than the respective Delta R-2 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 +/- 0.09 pg Gd per cell or 1.69 X 10(9) Gd3+ ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations <= 28 mu M Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R-2* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T. Copyright (C) 2010 John Wiley & Sons, Ltd.