COMPUTATIONAL MODELING OF CELLULAR EFFECTS POST-IRRADIATION WITH LOW- AND HIGH-LET PARTICLES AND DIFFERENT ABSORBED DOSES

The use of computational methods to improve the understanding of biological responses to various types of radiation is an approach where multiple parameters can be modelled and a variety of data is generated. This study compares cellular effects modelled for low absorbed doses against high absorbed doses. The authors hypothesized that low and high absorbed doses would contribute to cell killing via different mechanisms, potentially impacting on targeted tumour radiotherapy outcomes. Cellular kinetics following irradiation with selective low- and high-linear energy transfer (LET) particles were investigated using the Virtual Cell (VC) radiobiology algorithm. Two different cell types were assessed using the VC radiobiology algorithm: human fibroblasts and human crypt cells. The results showed that at lower doses (0.01 to 0.2 Gy), all radiation sources used were equally able to induce cell death (p\u3e0.05, ANOVA). On the other hand, at higher doses (1.0 to 8.0 Gy), the radiation response was LET and dose dependent (p\u3c0.05, ANOVA). The data obtained suggests that the computational methods used might provide some insight into the cellular effects following irradiation. The results also suggest that it may be necessary to re-evaluate cellular radiation-induced effects, particularly at low doses that could affect therapeutic effectiveness

Palliative treatment of metastatic bone pain with radiopharmaceuticals: a perspective beyond Strontium-89 and Samarium-153

PurposeThe present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond 89Sr and 153Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals.Materials and methodsA literature search was conducted on Science Direct and PubMed databases (1990 - 2015). The following search terms were combined in order to obtain relevant results: bone, metastases, palliative, care, therapy, treatment, radiotherapy, review, radiopharmaceutical, phosphorus-32, strontium-89, yttrium-90, tin-117m, samarium-153, holmium-166, thulium-170, lutetium-177, rhenium-186, rhenium-188 and radium-223. Studies were included if they provided information regarding the clinical outcomes.Results and conclusionsA comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patients life expectancy, radionuclides physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, 177Lu and 188Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively

Orchestration at the beginning: mitosis in sea urchin embryo

Development of multicellular organisms is driven by a series of mitotic divisions after fertilization. Total cytoplasmic volume does not increase during this process, resulting in an increasing number of smaller daughter cells. Cell divisions are initially synchronous in an early embryo, but this ends at the 16-cell stage in the sea urchin. Orchesterated mitosis does, however, continue in subpopulations via the coordination of two different processes: karyokinesis and cytokinesis. Part of this asynchrony is due to the differentiation of lineages.Fil: Abruzzese, Giselle Adriana. University of Chicago; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tanpradit, Nae. University of Chicago; Estados UnidosFil: Tavares, Renata S.. University of Chicago; Estados Unido

Positron Emission Tomography Techniques to Measure Active Inflammation, Fibrosis and Angiogenesis in Hypertensive Heart Failure

Heart failure, which is responsible for a high number of deaths worldwide, can develop due to chronic hypertension. Heart failure can involve and progress through several different pathways, including: fibrosis, inflammation, and angiogenesis. Early and specific detection of changes in the myocardium during the transition to heart failure can be made via the use of molecular imaging techniques, including positron emission tomography (PET). Traditional cardiovascular PET techniques, such as myocardial perfusion imaging and sympathetic innervation imaging, have been established at the clinical level but are often lacking in pathway and target specificity that is important for assessment of heart failure. Therefore, there is a need to identify new PET imaging markers of inflammation, fibrosis and angiogenesis that could aid diagnosis, staging and treatment of hypertensive heart failure. This review will provide an overview of key mechanisms underlying hypertensive heart failure and will present the latest developments in PET probes for detection of cardiovascular inflammation, fibrosis and angiogenesis. Currently, selective PET probes for detection of angiogenesis remain elusive but promising PET probes for specific targeting of inflammation and fibrosis are rapidly progressing into clinical use

Automated Radiosynthesis of cis- and trans-4-[18F]Fluoro-L-proline using [18F]Fluoride

The positron emission tomography imaging agents cis- and trans-4-[18F]fluoro-l-proline are used for the detection of numerous diseases such as pulmonary fibrosis and various carcinomas. These imaging agents are typically prepared by nucleophilic fluorination of 4-hydroxy-l-proline derivatives, with [18F]fluoride, followed by deprotection. Although effective radiofluorination reactions have been developed, the overall radiosynthesis process is suboptimal due to deprotection methods that are performed manually, require multiple steps, or involve harsh conditions. Here we describe the development of two synthetic routes that allow access to precursors, which undergo highly selective radiofluorination reactions and rapid deprotection, under mild acidic conditions. These methods were found to be compatible with automation, avoiding manual handling of radioactive intermediates

Parameterised Geant4 simulation for total body PET research

Total-body positron emission tomography (PET) imaging has the potential to transform medical care of a number of diseases and augment our knowledge of systems biology. Various detector designs and geometries are currently under development for total-body PET imaging of humans. This variety, in particular the variation in axial field-of-view (aFOV), motivates a need to compare the performance of these devices in a consistent simulated environment. We present an open-source Geant4 simulation package that allows variation of relevant parameters such as the detector aFOV and the tracer radioisotope from the command line. Two simplified detector geometries based on the Siemens Biograph Vision Quadra and United Imaging uEXPLORER models are supported with variable granularity. The intrinsic radioactivity of the detector crystals is fully simulated. The simulation can be viewed with the built-in GUI, and the results are saved in a plain text format for easy analysis. Example Python analysis code is provided with the simulation, demonstrating calculation of the noise equivalent count rate (NECR) figure of merit using an approximation to the NEMA NU 2-2012 standard method. A good agreement between the simulated count rate performance and experimental data is observed for both geometries. The differences in results are attributed to simplifications in the simulation code, namely not accounting for the light-collection efficiency or readout dead-time. We demonstrate the importance of assessing the scanner performance using appropriate phantom length which significantly affects the obtained results. A dependence between the detector aFOV and the length of the source, with peak NECR plateauing as the detector extends beyond the region of interest is also presented.Comment: 13 pages in total, 6 figure

Princípios gerais de culturas de células e citometria de fluxo para avaliação dos efeitos da radiação ionizante

Este relatório tem por objectivos expor em os princípios gerais de cultura de células e da citometria de fluxo para análise dos efeitos da radiação ionizante em culturas de células. Assim, conceitos relacionados com culturas de células, incluindo tipos de culturas e vantagens e desvantagens, são expostos no presente relatório. Adicionalmente, o princípio da técnica de citometria de fluxo, bem como, o seu uso em estudos dos efeitos da radiação ionizante em culturas de células, são igualmente apresentados.This report aims to explain in the basic principles of cells culture and flow citometry for the study of ionizing radiation effects on cells culture. Thus, subjects such as cells culture type and advantages/disadvantages of cells culture are explained. Additionally, basic principles of flow citometry, as well as, its applicability for the study of ionizing radiation effects on cell culture are also presented

In silico comparasion of 11 different radioisotopes for palliative treatment of bone metastases

Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology. However, the choice of which bone seeking agent to use is not consensual. Computer simulation is a simple and practical solution to study and to compare a variety of radioisotopes. This study aimed to compare 11 different radioisotopes currently in use or under research. Hence, computational models were used to estimate the percentage of deoxyribonucleic acid damage, the probability of correct DNA repair, and the radiation-induced cellular effects post-irradiation. 223Ra alpha particles, 177Lu beta minus particles, and 170Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by 89Sr and 153Sm, was higher than 177Lu beta minus particles and 223Ra alpha particles. Findings reported here may prompt future in vitro and in vivo experiments comparing different radionuclides for palliative treatment of bone metastases