A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study.

BACKGROUND: Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs. RESULTS: The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP. CONCLUSION: We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.

Sugar/gadolinium-loaded gold nanoparticles for labelling and imaging cells by magnetic resonance imaging.

Targeted magnetic resonance imaging (MRI) probes for selective cell labelling and tracking are highly desired. We here present biocompatible sugar-coated paramagnetic Gd-based gold nanoparticles (Gd-GNPs) and test them as MRI T1 reporters in different cellular lines at a high magnetic field (11.7 T). With an average number of 20 Gd atoms per nanoparticle, Gd-GNPs show relaxivity values r1 ranging from 7 to 18 mM-1 s-1 at 1.41 T. The multivalent presentation of carbohydrates on the Gd-GNPs enhances the avidity of sugars for carbohydrate-binding receptors at the cell surface and increases the local concentration of the probes. A large reduction in longitudinal relaxation times T1 is achieved with both fixed cells and live cells. Differences in cellular labelling are obtained by changing the type of sugar on the gold surface, indicating that simple monosaccharides and disaccharides are able to modulate the cellular uptake. These results stress the benefits of using sugars to produce nanoparticles for cellular labelling. To the best of our knowledge this is the first report on labelling and imaging cells with Gd-based gold nanoparticles which use simple sugars as receptor reporters.

Interfacial interactions in polymer-layered silicate nanocomposites.

Interactions between sodium montmorillonite (Na-MMT) and a variety of probes, some of which are intended to model components of a polyurethane system, have been studied. Particular attention was given to the effect of preadsorbed water on the adsorption behavior of the probes. Flow microcalorimetry (FMC), diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS), and wide-angle X-ray scattering (WAXS) were used to monitor the adsorption process. The probe set included alcohols, amines, ethers, poly(propylene glycol) monobutyl ethers (PPG), and 4-ethylphenyl isocyanate (4-EPI). FMC revealed that the preadsorbed water molecules on undried Na-MMT hindered the adsorption of alcohol and ether probes, but had little effect on the adsorption of amines. Drying of Na-MMT to less than 0.3% w/w H2O led to an increase in heat of adsorption and generally greater retention of the probes. PPG showed strong interaction with Na-MMT due to multipoint adsorption. With dried Na-MMT, WAXS revealed that PPG of molecular weight (MW) 1000 was partly intercalated into the gallery while lower molecular weight PPG (MW 340) did not intercalate the Na-MMT. DRIFTS spectra of 4-EPI adsorbed on undried Na-MMT revealed urea linkages, indicating formation of N,N'-bis(4-ethylphenyl) urea. In contrast, with dried Na-MMT the 4-EPI formed a urethane linkage with hydroxyl groups present at the edges of the silicate platelets.