Ultrasmall paramagnetic Gd
2O
3 nanoparticles have been developed as contrast agents for molecular and cellular preclinical MRI procedures. These small particles (mean diameter <5 nm) have the highest Gd density of all paramagnetic contrast agents. They generate strong positive contrast enhancement in
T1-weighted MRI. Signal enhancement is modulated by the interactions of water molecules with Gd, and very small particles provide the optimal surface-to-volume ratios necessary to reach high relaxivities. Conventional Gd
2O
3 nanocrystal synthesis techniques, and subsequent polyethylene glycol (PEG) grafting procedures are usually time-consuming and recovery losses are also limitative. The present study reports on a new, fast, and efficient one-pot Gd
2O
3 synthesis technique that provides PEGylated nanoparticles of very small size (mean diameter = 1.3 nm). Readily coated with PEG, the particles are colloidally stable in aqueous media and provide high longitudial relaxivities and small
r2/
r1 ratios (
r1 = 14.2 mM
鈥? s
鈥? at 60 MHz;
r2/
r1 = 1.20), ideal for
T1-weighted MRI. In this study, F98 brain cancer cells (glioblastoma multiforme) were labeled with the contrast agent and implanted in vivo (mice brains). The labeled cells appeared positively contrasted at least 48 h after implantation. Each one of the implanted animals developed a brain tumor. The performance of PEG-Gd
2O
3 was also compared with that of commercially available iron oxide nanoparticles. This study demonstrated that ultrasmall PEG-Gd
2O
3 nanoparticles provide strong positive contrast enhancement in
T1-weighted imaging, and allow the visualization of labeled cells implanted in vivo.
Keywords:
magnetic resonance imaging MRI; contrast agents; gadolinium oxide; nanoparticles; polyethylene glycol; cell labeling; cell tracking; glioblastoma multiforme