Our study describes the time course of necrotic damage to the rat brain resulting from Leksell Gamma Knife (LGK) irradiation at a dose that was previously considered to be subnecrotic. A lesion induced in the rat hippocampus by 35 Gy irradiation was monitored by MRI, MRS, and DW‐MRI for 16 months. T₂‐weighted images revealed a large hyperintense area with an increased apparent diffusion coefficient of water (ADC_w), which occurred 8 months after irradiation, accompanied by metabolic changes (increase of lactate (Lac) and choline (Cho), and decrease of creatine (Cr) and N‐acetyl aspartate (NAA), as determined by MRS) that indicated an edema. In two animals, the hyperintensity persisted and a postnecrotic cavity connected to enlarged lateral ventricles developed. In the rest of the animals, the hyperintensity started to decrease 9 months post‐irradiation (PI), revealing hypointense areas with a decreased ADC_w. Histology confirmed the MRI data, showing either scar formation or the development of a postnecrotic cavity. Magn Reson Med 52:397–402, 2004.

Upconverting nanoparticles (UCNPs) are of particular interest in nanomedicine for in vivo deep-tissue optical cancer bioimaging due to their efficient cellular uptake dependent on polymer coating. In this study, particles, ca. 25 nm in diameter, were prepared by a high-temperature coprecipitation of lanthanide chlorides. To ensure optimal dispersion of UCNPs in aqueous milieu, they were coated with three different polymers containing reactive groups, i.e., poly(ethylene glycol)-alendronate (PEG-Ale), poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide)-alendronate (PDMA-Ale), and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). All the particles were characterized by TEM, DLS, FTIR, and spectrofluorometer to determine the morphology, hydrodynamic size and ξ-potential, composition, and upconversion luminescence. The degradability/dissolution of UCNPs in water, PBS, DMEM, or artificial lysosomal fluid (ALF) was evaluated using an ion-selective electrochemical method and UV-Vis spectroscopy. The dissolution that was more pronounced in PBS at elevated temperatures was decelerated by polymer coatings. The dissolution in DMEM was relatively small, but much more pronounced in ALF. PMVEMA with multiple anchoring groups provided better protection against particle dissolution in PBS than PEG-Ale and PDMA-Ale polymers containing only one reactive group. However, the cytotoxicity of the particles depended not only on their ability to rapidly degrade, but also on the type of coating. According to MTT, neat UCNPs and UCNP@PMVEMA were toxic for both rat cells (C6) and rat mesenchymal stem cells (rMSCs), which was in contrast to the UCNP@Ale-PDMA particles that were biocompatible. On the other hand, both the cytotoxicity and uptake of the UCNP@Ale-PEG particles by C6 and rMSCs were low, according to MTT assay and ICP-MS, respectively. This was confirmed by a confocal microscopy, where the neat UCNPs were preferentially internalized by both cell types, followed by the UCNP@PMVEMA, UCNP@Ale-PDMA, and UCNP@Ale-PEG particles. This study provides guidance for the selection of a suitable nanoparticle coating with respect to future biomedical applications where specific behaviors (extracellular deposition vs. cell internalization) are expected.

Multimodal imaging, integrating several modalities including down- and up-conversion luminescence, T₁- and T₂(T₂*)-weighted MRI, and CT contrasting in one system, is very promising for improved diagnosis of severe medical disorders. To reach the goal, it is necessary to develop suitable nanoparticles that are highly colloidally stable in biologically relevant media. Here, hydrophilic poly(N,N-dimethylacrylamide-N-acryloylglycine methyl ester)-alendronate-[P(DMA-AGME)-Ale]-coated Gd(Tb)F₃:Tb³⁺(Gd³⁺),Yb³⁺,Nd³⁺ nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) followed by coating with the polymer. The particles were tho-roughly characterized by a dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray energy dispersive spectroscopy (EDAX), selected area electron diffraction (SAED), elemental ana-lysis and fluorescence spectroscopy. Aqueous particle dispersions exhibited excellent colloidal stability in water and physiological buffers. In vitro toxicity assessments suggested no or only mild toxicity of the surface-engineered Gd(Tb)F₃:Tb³⁺(Gd³⁺),Yb³⁺,Nd³⁺ particles in a wide range of concentrations. Internalization of the particles by several types of cells, including HeLa, HF, HepG2, and INS, was confirmed by a down- and up-conversion confocal microscopy. Newly developed particles thus proved to be an efficient contrast agent for fluorescence imaging, T₁- and T₂(T₂*)-weighted magnetic resonance imaging (MRI), and computed tomography (CT).

A wise selection of tracers is critical for magnetic particle imaging (MPI). Most of the current tracers are based on superparamagnetic iron oxide nanoparticles (SPIONs) with a suitable coating. We prepared maghemite cores (γ-Fe₂O₃) by coprecipitation of Fe(II) and Fe(III) salts with ammonium hydroxide followed by oxidation with hydrogen peroxide and stabilization as an anionic (γ-Fe₂O₃^⊖) or cationic colloid (γ-Fe₂O₃^⨁). The cores were coated by poly(N-(2-hydroxypropyl)methacrylamide)-co-N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide. The particles were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, Mössbauer spectroscopy, tested in vitro in a field-free point MPI scanner, and compared to nanoparticles prepared by oxidation with sodium hypochlorite and to the commercially available Resovist®. The cores had an average diameter of 8.0 nm (γ-Fe₂O₃^⨁) and 8.7 nm (γ-Fe₂O₃^⊖); the hydrodynamic diameter was 88 nm. Zeta potential values for both positively charged (+52 mV) and negatively charged particles (–60 mV) provided for good colloidal stabilization. Spinel structure of maghemite was confirmed by Mössbauer spectroscopy. The uncoated γ-Fe₂O₃^⨁ particles yielded an MPI signal lower (by 16 %) than Resovist; the coated ones reached 88 % of the Resovist signal. Anionic γ-Fe₂O₃^⊖ particles reached a higher (uncoated particles, by 15 %) or comparable (coated ones) signal relative to Resovist with a substantially lower signal dispersion. Control particles prepared by oxidation with sodium hypochlorite scored the weakest results. To conclude, a suitable size, narrow size distribution, and colloidal stability predispose the synthetized particles for use as a tracer for MPI. The anionic particles provided a higher signal with a lower dispersion than commercial tracers.