PSMA-targeting iron oxide magnetic nanoparticles enhance MRI of preclinical prostate cancer

Aim Evaluate potential of newly-developed, biocompatible iron oxide magnetic nanoparticles (MNPs) conjugated with J591, an antibody to an extracellular epitope of prostate specific membrane antigen (PSMA), to enhance MRI of prostate cancer (PCa). Materials & Methods Specific binding to PSMA by J591-MNP was investigated in vitro. MRI studies were performed on orthotopic tumor-bearing NOD.SCID mice 2h and 24hr after intravenous injection of J591-MNPs, or non-targeting MNPs. Results and Conclusions In vitro, MNPs did not affect PCa cell viability, and conjugation to J591 did not compromise antibody specificity and enhanced cellular iron uptake. In vivo, PSMA-targeting MNPs increased MR contrast of tumors, but not by non-targeting MNPs. This provides proof-of-concept that PSMA-targeting MNPs have potential to enhance MR detection/localization of PCa.,

Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

Including nonequilibrium interface kinetics in a continuum model for melting nanoscaled particles

The melting temperature of a nanoscaled particle is known to decrease as the curvature of the solid-melt interface increases. This relationship is most often modelled by a Gibbs--Thomson law, with the decrease in melting temperature proposed to be a product of the curvature of the solid-melt interface and the surface tension. Such a law must break down for sufficiently small particles, since the curvature becomes singular in the limit that the particle radius vanishes. Furthermore, the use of this law as a boundary condition for a Stefan-type continuum model is problematic because it leads to a physically unrealistic form of mathematical blow-up at a finite particle radius. By numerical simulation, we show that the inclusion of nonequilibrium interface kinetics in the Gibbs--Thomson law regularises the continuum model, so that the mathematical blow up is suppressed. As a result, the solution continues until complete melting, and the corresponding melting temperature remains finite for all time. The results of the adjusted model are consistent with experimental findings of abrupt melting of nanoscaled particles. This small-particle regime appears to be closely related to the problem of melting a superheated particle.

Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Polymer-mediated synthesis of γ-Fe2O3 nano-particles

Nano-particles of γ-Fe2O3 were synthesized by reacting polyethylene oxide–FeCl3 complex with NH4OH. These were characterized by X-ray diffraction (XRD), scanning electron miscroscopy (SEM), selected area electron diffraction (SAED) and transmision electron microscopy (TEM). The average particle size was found to be 10 nm, as determined from the line broadening of the main XRD peak. The crystalline phase was a spinel-type tetragonal structure, which was confirmed from the electron diffraction pattern. The zero field cooled magnetization of samples with varying γ-Fe2O3 content as a function of temperature was measured using a vibrating sample magnetometer. The magnetization curves show a peak at low temperature (15 K) corresponding to the blocking temperature TB. The value of TB was found to decrease with decreasing particle size. The magnetization measurements with respect to field at 5 and 170 K confirmed the transition from superparamagnetic to spin-glass state at TB, as evidenced from the remanence and hysteresis. These results can be explained on the basis of Néel's theory of superparamagnetism as applied to nano-particles.

Investigations of ultrafine particles emitted by ships and other transport modes in the port of Brisbane

This research measured particle and gaseous emissions from ships and trains operating within the Port of Brisbane, and explored their influence on ambient air composition at a downwind suburban measurement site. The ship and train emission factor investigations resulted in the development of novel measurement techniques which permit the quantification of particle and gaseous emission factors using samples collected from post-emission exhaust plumes. The urban influence investigation phase of the project produced a new approach to identifying influences from ship emissions.

Molecular camouflage : making use of protecting groups to control the self-assembly of inorganic janus particles onto metal–chalcogenide nanotubes by Pearson Hardness

Hard and soft: Binding of inorganic Pt@Fe3O4 Janus particles to WS2 nanotubes through their Pt or Fe3O4 domains is governed by the difference in Pearson hardness: the soft Pt block has a higher sulfur affinity than the harder magnetite face; thus the binding proceeds preferentially through the Pt face. This binding preference can be reversed by masking the Pt face with an organic protecting group.

An Australian perspective on the ALI-III global principles for cooperation in International insolvency cases

In 2012, Professor Ian Fletcher (United Kingdom) and Professor Bob Wessels (The Netherlands) presented a Report to the American Law Institute and the International Insolvency Institute entitled Transnational Insolvency: Global Principles for Cooperation in International Insolvency Cases (“Global Principles”). This followed their appointment as Joint Reporters to investigate whether the essential provisions of the American Law Institute Principles of Cooperation among the North American Free Trade Agreement Countries with their annexed Guidelines Applicable to Court-to-Court Communication in Cross-border Cases may, with certain necessary modifications, be acceptable for use by jurisdictions across the world. This article comments on the Global Principles from the perspective of a jurisdiction which has adopted the UNCITRAL Model Law on Cross-border Insolvency (“Model Law”). In 2008, Australia enacted a standalone statute, the Cross-border Insolvency Act 2008 (Cth) to which is annexed the Model Law. In that process, it made minimal changes to the Model Law text. Against the background of the 2008 Act, related procedural laws as well as Australia’s general insolvency statutes and recent cross-border insolvency jurisprudence, this article comments on the potential relevance of the Transnational Insolvency Report as a point of reference for Australian courts and insolvency administrators when addressing international insolvency cases. By comparing the Global Principles with the Model Law as closely adopted in Australia, this analysis is a resource for other Model Law jurisdictions when considering the potential relevance of the Global Principles for their own international insolvency practice.

Adsorption and mobility of metals in build-up on road surfaces

The study investigated the adsorption and bioavailability characteristics of traffic generated metals common to urban land uses, in road deposited solids particles. To validate the outcomes derived from the analysis of field samples, adsorption and desorption experiments were undertaken. The analysis of field samples revealed that metals are selectively adsorbed to different charge sites on solids. Zinc, copper, lead and nickel are adsorbed preferentially to oxides of manganese, iron and aluminium. Lead is adsorbed to organic matter through chemisorption. Cadmium and chromium form weak bonding through cation exchange with most of the particle sizes. Adsorption and desorption experiments revealed that at high metal concentrations, chromium, copper and lead form relatively strong bonds with solids particles while zinc is adsorbed through cation exchange with high likelihood of being released back into solution. Outcomes from this study provide specific guidance for the removal of metals from stormwater based on solids removal.

Stefan problems for melting nanoscaled particles

Under certain conditions, the mathematical models governing the melting of nano-sized particles predict unphysical results, which suggests these models are incomplete. This thesis studies the addition of different physical effects to these models, using analytic and numerical techniques to obtain realistic and meaningful results. In particular, the mathematical "blow-up" of solutions to ill-posed Stefan problems is examined, and the regularisation of this blow-up via kinetic undercooling. Other effects such as surface tension, density change and size-dependent latent heat of fusion are also analysed.

Degradation of hydroxycinnamic acid mixtures in aqueous sucrose solutions by the Fenton process

The degradation efficiencies and behaviors of caffeic acid (CaA), p-coumaric acid (pCoA) and ferulic acid (FeA) in aqueous sucrose solutions containing the mixture of these hydroxycinnamic acids (HCAs) mixtures were studied by the Fenton oxidation process. Central composite design and multi-response surface methodology were used to evaluate and optimize the interactive effects of process parameters. Four quadratic polynomial models were developed for the degradation of each individual acid in the mixture and the total HCAs degraded. Sucrose was the most influential parameter that significantly affected the total amount of HCA degraded. Under the conditions studied there was < 0.01% loss of sucrose in all reactions. The optimal values of the process parameters for a 200 mg/L HCA mixture in water (pH 4.73, 25.15 °C) and sucrose solution (13 mass%, pH 5.39, 35.98 °C) were 77% and 57% respectively. Regression analysis showed goodness of fit between the experimental results and the predicted values. The degradation behavior of CaA differed from those of pCoA and FeA, where further CaA degradation is observed at increasing sucrose and decreasing solution pH. The differences (established using UV/Vis and ATR-FTIR spectroscopy) were because, unlike the other acids, CaA formed a complex with Fe(III) or with Fe(III) hydrogen-bonded to sucrose, and coprecipitated with lepidocrocite, an iron oxyhydroxide.

Charged particles and cluster ions produced during cooking activities

Previous studies showed that a significant number of the particles present in indoor air are generated by cooking activities, and measured particle concentrations and exposures have been used to estimate the related human dose. The dose evaluation can be affected by the particle charge level which is usually not considered in particle deposition models. To this purpose, in this paper we show, for the very first time, the electric charge of particles generated during cooking activities and thus extending the interest on particle charging characterization to indoor micro-environments, so far essentially focused on outdoors. Particle number, together with positive and negative cluster ion concentrations, was monitored using a condensation particle counter and two air ion counters, respectively, during different cooking events. Positively-charged particle distribution fractions during gas combustion, bacon grilling, and eggplant grilling events were measured by two Scanning Mobility Particle Sizer spectrometers, used with and without a neutralizer. Finally, a Tandem Differential Mobility Analyzer was used to measure the charge specific particle distributions of bacon and eggplant grilling experiments, selecting particles of 30, 50, 80 and 100 nm in mobility diameter. The total fraction of positively-charged particles was 4.0%, 7.9%, and 5.6% for gas combustion, bacon grilling, and eggplant grilling events, respectively, then lower than other typical outdoor combustion-generated particles.

Elemental composition of ambient fine particles in urban schools : sources of children’s exposure

Currently, there is a limited understanding of the sources of ambient fine particles that contribute to the exposure of children at urban schools. Since the size and chemical composition of airborne particle are key parameters for determining the source as well as toxicity, PM1 particles (mass concentration of particles with an aerodynamic diameter less than 1 µm) were collected at 24 urban schools in Brisbane, Australia and their elemental composition determined. Based on the elemental composition four main sources were identified; secondary sulphates, biomass burning, vehicle and industrial emissions. The largest contributing source was industrial emissions and this was considered as the main source of trace elements in the PM1 that children were exposed to at school. PM1 concentrations at the schools were compared to the elemental composition of the PM2.5 particles (mass concentration of particles with an aerodynamic diameter less than 2.5 µm) from a previous study conducted at a suburban and roadside site in Brisbane. This comparison revealed that the more toxic heavy metals (V, Cr, Ni, Cu, Zn and Pb), mostly from vehicle and industrial emissions, were predominantly in the PM1 fraction. Thus, the results from this study points to PM1 as a potentially better particle size fraction for investigating the health effects of airborne particles.