Observation of dose-rate dependence in a Fricke dosimeter irradiated at low dose rates with monoenergetic X-rays

<p>Absolute measurements of the radiolytic yield of Fe3+ in a ferrous sulphate dosimeter formulation (6 mM Fe2+), with a 20 keV x-ray monoenergetic beam, are reported. Dose-rate suppression of the radiolytic yield was observed at dose rates lower than and different in nature to those previously reported with x-rays. We present evidence that this effect is most likely to be due to recombination of free radicals radiolytically produced from water. The method used to make these measurements is also new and it provides radiolytic yields which are directly traceable to the SI standards system. The data presented provides new and exacting tests of radiation chemistry codes.</p

Resurgence of a Nation’s Radiation Science Driven by Its Nuclear Industry Needs

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-26, pub-electronic 2021-11-23Publication status: PublishedThis article describes the radiation facilities and associated sample preparation, management, and analysis equipment currently in place at the Dalton Cumbrian Facility, a facility which opened in 2011 to support the UK’s nuclear industry. Examples of measurements performed using these facilities are presented to illustrate their versatility and the breadth of research they make possible. Results are presented from research which furthers our understanding of radiation damage to polymeric materials, radiolytic yield of gaseous products in situations relevant to nuclear materials, radiation chemistry in light water reactor cooling systems, material chemistry relevant to immobilization of nuclear waste, and radiation-induced corrosion of fuel cladding elements. Applications of radiation chemistry relevant to health care are also described. Research concerning the mechanisms of radioprotection by dietary carotenoids is reported. An ongoing open-labware project to develop a suite of modular sample handling components suited to radiation research is described, as is the development of a new neutron source able to provide directional beams of neutrons

Imaging intracellular and systemic in vivo gold nanoparticles to enhance radiotherapy

Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both kilo-electron-volt and mega-electron-volt X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumours. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumour samples. Spatially accurate imaging on the nanoscale poses a serious challenge requiring high- or super-resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitizers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our own work, we have used multiphoton excited plasmon resonance imaging to map the AuNP intracellular distribution. The benefits and limitations of this approach will also be discussed in some detail. In some cases, the same “excitation” mechanism as is used in an imaging modality can be harnessed to make it also a part of therapy modality (e.g. phototherapy)—such examples are discussed in passing as extensions to the imaging modality concerned

S1 Appendix. Mathematical appendix and full derivations. from Oxygen diffusion in ellipsoidal tumour spheroids

Oxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multicellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of <i>in vitro</i> experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions breakdown remains unanswered. In this work, we derive equations governing oxygen distribution (and more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality

On the Equivalence of the Biological Effect Induced by Irradiation of Clusters of Heavy Atom Nanoparticles and Homogeneous Heavy Atom-Water Mixtures

A multiscale local effect model (LEM)-based framework was implemented to study the cell damage caused by the irradiation of clusters of gold nanoparticles (GNPs) under clinically relevant conditions. The results were compared with those obtained by a homogeneous mixture of water and gold (MixNP) irradiated under similar conditions. To that end, Monte Carlo simulations were performed for the irradiation of GNP clusters of different sizes and MixNPs with a 6 MV Linac spectrum to calculate the dose enhancement factor in water. The capabilities of our framework for the prediction of cell damage trends are examined and discussed. We found that the difference of the main parameter driving the cell damage between a cluster of GNPs and the MixNP was less than 1.6% for all cluster sizes. Our results demonstrate for the first time a simple route to intuit the radiobiological effects of clusters of nanoparticles through the consideration of an equivalent homogenous gold/water mixture. Furthermore, the negligible difference on cell damage between a cluster of GNPs and MixNP simplifies the modelling for the complex geometries of nanoparticle aggregations and saves computational resources

Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams

PurposeTo investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams.Methods and MaterialsHuman skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, and distal positions of SOBP and the entrance and peak position for the pristine beam.ResultsA significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci.ConclusionsThe DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions

S2 Appendix. Sample code for ellipsoid oxygen distribution and OCR 287 calculation (Mathematica, MATLAB / Octave, Excel spreadsheet) from Oxygen diffusion in ellipsoidal tumour spheroids

Oxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multicellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of <i>in vitro</i> experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions breakdown remains unanswered. In this work, we derive equations governing oxygen distribution (and more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality