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Simple Summary: Neuroblastoma is a common pediatric cancer that spreads systemically, making therapy difficult. Tumors are frequently resistant to radiation therapy, a last line of defense in patients with aggressive disease. In this study, we found that there are distinct gene expression patterns dependent on neuroblastoma subtype; however, both neuroblastoma types examined showed only subtle gene expression differences early following radiation exposure. This indicates that while neuroblastoma tumors are diverse in phenotype and gene expression, they have similarly stable gene expression and resistance during early response to stressors such as radiation. Abstract: External beam radiation is infrequently used for treatment of pediatric cancer such as neuroblastoma, typically reserved for palliative care in patients with aggressive metastatic disease who fail to respond to alternative treatments. Understanding effects of radiation on neuroblastoma cells could improve efficacy of this final means of therapy to decrease tumor burden and stabilize the disease. In this study, clonogenic assays were used to establish radiation responses for SK-N-AS and SK-N-DZ cell lines; cells were then irradiated at doses that cause 90% cell killing based on clonogenic assay and their RNA isolated and subjected to microarray analysis. In addition, cells were transfected with pre-miRNA constructs that led to overexpression of microRNAs miR-34a and miR-1228. Statistically significant differences were detected for expression of several thousands of genes when the two cell lines were compared with each other. In comparison, radiation led only to minor gene expression differences of less than two-fold at the 1h post-irradiation timepoint in both cell lines. Overexpression of miR-34a and miR-1228 in either cell line did not change this outcome. Therefore, neuroblastoma cell lines SK-N-AS and SK-N-DZ are phenotypically diverse and gene expression differences between them are extensive. At the same time, the regulation of gene expression in both of these cell lines is in a stable equilibrium at early timepoints after exposure to ionizing radiation.

In this commentary we consider the importance of ready access to ecological data, existing resources and approaches for radiological datasets and material, and wider public policy developments in regard to data access and reuse. We describe the development and operation of the STORE database for radiobiology, radioecology and epidemiology as a central data sharing resource, and finally we consider the issues of financial and scientific sustainability of material resource archives and the future of resources like STORE.

Scanning X-ray fluorescence (XRF) tomography provides powerful characterization capabilities in evaluating elemental distribution and differentiating their inter- and intra-cellular interactions in a three-dimensional (3D) space. Scanning XRF tomography encounters practical challenges from the sample itself, where the range of rotation angles is limited by geometric constraints, involving sample substrates or nearby features either blocking or converging into the field of view. This study aims to develop a reliable and efficient workflow that can (1) expand the experimental window for nanoscale tomographic analysis of local areas of interest within a laterally extended specimen, and (2) bridge 3D analysis at micrometer and nanoscales on the same specimen. We demonstrate the workflow using a specimen of HeLa cells exposed to iron oxide core and titanium dioxide shell (Fe3O4/TiO2) nanocomposites. The workflow utilizes iterative and multiscale XRF data collection with intermediate sample processing by focused ion beam (FIB) sample preparation between measurements at different length scales. Initial assessment combined with precise sample manipulation via FIB allows direct removal of sample regions that are obstacles to both incident X-ray beam and outgoing XRF signals, which considerably improves the subsequent nanoscale tomography analysis. This multiscale analysis workflow has advanced bio-nanotechnology studies by providing deep insights into the interaction between nanocomposites and single cells at a subcellular level as well as statistical assessments from measuring a population of cells.

In developing a cluster-nanocarrier design, as a magnetic resonance imaging contrast agent, we have investigated the enhanced relaxivity of a manganese and iron-oxo cluster grafted within a porous polystyrene nanobead with increased relaxivity due to a higher surface area. The synthesis of the cluster-nanocarrier for the cluster Mn

Magnetic resonance imaging (MRI) has received significant attention as the noninvasive diagnostic technique for complex diseases. Image-guided therapeutic strategy for diseases such as cancer has also been at the front line of biomedical research, thanks to the innovative MRI, enhanced by the prior delivery of contrast agents (CAs) into patients' bodies through injection. These CAs have contributed a great deal to the clinical utility of MRI but have been based on metal-containing compounds such as gadolinium, manganese, and iron oxide. Some of these CAs have led to cytotoxicities such as the incurable Nephrogenic Systemic Fibrosis (NSF), resulting in their removal from the market. On the other hand, CAs based on organic nitroxide radicals, by virtue of their structural composition, are metal free and without the aforementioned drawbacks. They also have improved biocompatibility, ease of functionalization, and long blood circulation times, and have been proven to offer tissue contrast enhancement with longitudinal relaxivities comparable with those for the metal-containing CAs. Thus, this Review highlights the recent progress in metal-based CAs and their shortcomings. In addition, the remarkable goals achieved by the organic nitroxide radical CAs in the enhancement of MR images have also been discussed extensively. The focal point of this Review is to emphasize or demonstrate the crucial need for transition into the use of organic nitroxide radicals-metal-free CAs-as against the metal-containing CAs, with the aim of achieving safer application of MRI for early disease diagnosis and image-guided therapy.

Trace elements, particularly metals, play an important role in a large variety of cellular processes in a biological system. In the context of biological organisms and tissues, the term trace element means that over the entire organism an element is present at only trace levels, say 100 ppm or lower. Trace element distribution and content can be analyzed using several techniques, for example, visible light optical fluorescence imaging, energy-dispersive x-ray spectroscopy on an electron microscope, synchrotron-based x-ray fluorescence (XRF) imaging, secondary-ion mass spectrometry, and laser ablation inductively coupled with mass spectrometry. Comprehensive reviews on these techniques are given by Lobinski et al. [1] and McRae et al. [2]. Among these techniques, synchrotron-based XRF microscopy, particularly utilizing third-generation x-ray sources and advanced x-ray focusing optics, offers the most suitable capabilities to perform trace element studies of biological samples: The penetrating power and non-destructive nature of x-rays allows one to image many-micron-thick biological samples such as biological whole cells in a way that visible light or electron microscopes cannot; the sensitivity of x-ray-induced XRF is down to parts per million, several orders of magnitude better than standard electron-based techniques due to the absence of bremsstrahlung background in x-ray-induced x-ray emission. The capability of imaging frozen samples in both 2D and 3D with sub-50 nm resolution in various x-ray modes has greatly advanced a broad range of scientific studies. This article describes how this technique can be used to track the incorporation of nanocomposites into cancer cells.

We are developing TiO2 nanoconjugates that can be used as therapeutic and diagnostic agents. Nanoscale TiO2 can be surface conjugated with various molecules and has the unique ability to induce the production of reactive oxygen species after radiation activation. One way to improve the potential clinical usefulness of TiO2 nanoparticles is to control their delivery to malignant cells by targeting them to cancer cell specific antigens. Epidermal Growth Factor Receptor is one potential target that is enriched in epithelial cancers and is rapidly internalized after ligand binding. Hence, we have synthesized TiO2 nanoparticles and functionalized them with a short EGFR binding peptide to create EGFR-targeted NCs. X-ray Fluorescence Microscopy was used to image nanoconjugates within EGFR positive HeLa cells. Further labeling of fixed cells with antibodies against EGFR and Protein A nanogold showed that TiO2 nanoconjugates can colocalize with receptors at the cell’s plasma membrane. Interestingly, with increased incubation times, EGFR targeted nanoconjugates could also be found colocalized with EGFR within the cell nucleus. This suggests that EGFR-targeted nanoconjugates can bind the receptor at the cell membrane, which leads to the internalization of NC-receptor complexes and the subsequent transport of nanoconjugates into the nucleus.

As a part of Radiation research conference, a workshop was held on life-long exposure studies conducted in the course of irradiation experiements done at Argonne National Laboratory between 1952-1992. A recent review article documents many of the issues discussed at that workshop.

We sought to test the hypothesis that transcatheter hepatic artery delivery of dilute gadolinium (Gd) in rabbits can be monitored in real-time using magnetic resonance imaging (MRI).Catheters (2F) were inserted via a femoral access into the hepatic arteries of six New Zealand White rabbits under radiographic guidance. After transfer to a 1.5-T MRI scanner, 26 separate hepatic artery injections of 2 mL of 4% Gd and 14 sham injections were performed. Real-time imaging of all injections was acquired using two-dimensional projection inversion recovery-gradient echo. Films of these 40 injections, as well as 10 random repeats, were independently reviewed in a randomized, blinded fashion by two Certificate of Added Qualification-certified interventional radiologists. Observers reported (i) if Gd injection occurred and (ii) if so, the location of delivery. For each observer, we compared sensitivity/specificity for real-time visualization of contrast injection and accuracy of injection localization. Interobserver and intraobserver variability was assessed using the kappa statistic. X-ray digital subtraction angiography was the gold standard for all MRI studies.Both observers had a sensitivity of 100% and a specificity of 93%. Accuracy for intrahepatic contrast delivery was 77% for both observers. Accuracy for extrahepatic delivery was 92% and 96%, respectively. Both interobserver and intraobserver agreement was outstanding.In rabbits, MRI allows for accurate real-time monitoring of transcatheter hepatic artery delivery of contrast agent. Localization accuracy is higher outside the liver than within the liver. These results can be used as a baseline reference for comparing the accuracy of delivery of Gd-tagged therapies in the future.