Uniform and extremely small-sized iron oxide nanoparticles (ESIONs) of < 4 nm were synthesized via the thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. Oleyl alcohol lowered the reaction temperature by reducing iron-oleate complex, resulting in the production of small-sized nanoparticles. XRD pattern of 3 nm-sized nanoparticles revealed maghemite crystal structure. These nanoparticles exhibited very low magnetization derived from the spin-canting effect. The hydrophobic nanoparticles can be easily transformed to water-dispersible and biocompatible nanoparticles by capping with the poly(ethylene glycol)-derivatized phosphine oxide (PO-PEG) ligands. Toxic response was not observed with Fe concentration up to 100 μg/mL in MTT cell proliferation assay of POPEG-capped 3 nm-sized iron oxide nanoparticles. The 3 nm-sized nanoparticles exhibited a high r(1) relaxivity of 4.78 mM(-1) s(-1) and low r(2)/r(1) ratio of 6.12, demonstrating that ESIONs can be efficient T(1) contrast agents. The high r(1) relaxivities of ESIONs can be attributed to the large number of surface Fe(3+) ions with 5 unpaired valence electrons. In the in vivo T(1)-weighted magnetic resonance imaging (MRI), ESIONs showed longer circulation time than the clinically used gadolinium complex-based contrast agent, enabling high-resolution imaging. High-resolution blood pool MR imaging using ESIONs enabled clear observation of various blood vessels with sizes down to 0.2 mm. These results demonstrate the potential of ESIONs as T(1) MRI contrast agents in clinical settings.

The theoretically predicted maximum r(2) relaxivity of iron oxide nanoparticles was achieved by optimizing the overall size of ferrimagnetic iron oxide nanocubes. Uniform-sized iron oxide nanocubes with an edge length of 22 nm, encapsulated with PEG-phospholipids (WFION), exhibited high colloidal stability in aqueous media. In addition, WFIONs are biocompatible and did not affect cell viability at concentrations up to 0.75 mg Fe/ml. Owing to the enhanced colloidal stability and the high r(2) relaxivity (761 mM(-1) s(-1)), it was possible to successfully perform in vivo MR imaging of tumors by intravenous injection of 22-nm-sized WFIONs, using a clinical 3-T MR scanner.

Dual-modal in vivo tumor imaging and photodynamic therapy using hexagonal NaYF(4):Yb,Er/NaGdF(4) core-shell upconverting nanoparticles combined with a photosensitizer, chlorin e6, is reported. Tumors can be clearly observed not only in the upconversion luminescence image but also in the magnetic resonance image. In vivo photodynamic therapy by systemic administration is demonstrated under 980 nm irradiation.

For ultrasensitive magnetic resonance imaging (MRI), magnetic nanoparticles with extremely high r2 relaxivity are strongly desired. Magnetosome-like nanoparticles were prepared by coating polyethylene glycol-phospholipid (PEG-phospholipid) onto ferrimagnetic iron oxide nanocubes (FIONs). FIONs exhibited a very high relaxivity (r2) of 324 mM −1 s −1 , allowing efficient labeling of various kinds of cells. The magnetic resonance (MR) imaging of single cells labeled with FIONs is demonstrated not only in vitro but also in vivo. Pancreatic islet grafts and their rejection could be imaged using FIONs on a 1.5 T clinical MRI scanner. The strong contrast effect of FIONs enabled MR imaging of transplanted islets in small rodents as well as in large animals. Therefore, we expect that MR imaging of pancreatic islet grafts using FIONs has the potentials for clinical applications. Furthermore, FIONs will enable highly sensitive noninvasive assessment after cell transplantation.cell tracking | contrast agent | molecular imaging | diabetes | islet transplantation

BACKGROUND AND PURPOSE:Dynamic contrast-enhanced T1-weighted perfusion MR imaging is much less susceptible to artifacts, and its high spatial resolution allows accurate characterization of the vascular microenvironment of the lesion. The purpose of this study was to test the predictive value of the initial and final area under the time signal-intensity curves ratio derived from dynamic contrastenhanced perfusion MR imaging to differentiate pseudoprogression from early tumor progression in patients with glioblastomas.