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1.
Int J Biol Macromol ; 263(Pt 2): 130332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401580

RESUMO

Glycogen, a complex branched glucose polymer and a blood-sugar reservoir in animals, comprises small ß particles joined together into composite α particles. In diabetic animals, α particles fragment more easily than those in healthy animals. Finding evidence for or against postulated mechanisms for α-particle formation is thus important for diabetes research. Insight into this is obtained here using Monte-Carlo simulations, including addition and loss of glucose monomer, branching and debranching, based on earlier simulations which were in acceptable agreement with experiment [Zhang et al., Int J Biol Macromolecules 2018, 116, 264]. One postulated mechanism for α-particle formation is "budding": occasionally a glucan chain temporarily protrudes from the particle, and if its growing end is sufficiently far from its parent particle, it propagates to a new linked particle. We tested this by simulations in which an "artificial" bud (a chain extending well outside the average particle radius) is added to a glycogen molecule in a dynamic steady state, and the system allowed to evolve. In some simulations, the particle reached a new steady state having an irregular dumbbell shape: a rudimentary α particle. Thus 'budding' is a possible mechanism for α particles to form. If no simulations had shown this behaviour, it would have refuted the postulate.


Assuntos
Diabetes Mellitus , Glicogênio , Animais , Partículas alfa , Glucose , Glicemia
2.
Anticancer Res ; 44(3): 879-888, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423627

RESUMO

Prostate cancer (PCa) is the most prevalent malignancy and leading cause of mortality in men. Despite the development of various drugs, such as novel androgen receptor signaling inhibitors and poly adenosine diphosphate-ribose polymerase inhibitors targeting homologous recombination repair-related genetic mutations, prognosis of metastatic castration-resistant prostate cancer remains unfavorable. However, recent advances in nuclear medicine have allowed for both imaging diagnostics and therapeutic interventions by targeting molecules specifically expressed in cancer cells with radioisotopes (RI). γ-rays are used in nuclear medicine imaging, whereas in therapy, α or ß-emitting RIs are administered to target cells in radiation therapy. PCa, in particular, exhibits the characteristic features of radioligand therapy, as the membrane protein prostate-specific membrane antigen (PSMA) is proportionally highly expressed in malignancy compared to normal tissues. The administered RI-labeled compound binds to PSMA, enabling specific targeting of PCa for treatment. Unlike ß-rays, α-rays have a shorter range and impart stronger energy to DNA, allowing α-particles to exhibit a higher linear energy transfer. Due to such characteristics, PSMA-targeted α radiotherapy is expected to have potent cytotoxic effects and fewer side effects on normal organs, making them more likely to be widely adopted in the future. However, reports on PSMA-targeted α radiotherapy differ in aspects, such as prior PSMA-targeted ß radiotherapy, the administered doses, and the number of treatment cycles. Therefore, in this review, we compile the reports on treatments utilizing α-emitting isotopes targeting PSMA in patients with PCa.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Próstata , Neoplasias da Próstata/radioterapia , Partículas alfa/uso terapêutico , Raios gama , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do Tratamento
3.
J Environ Radioact ; 273: 107392, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342022

RESUMO

The measurement of 226Ra and the identification of 226Ra-bearing minerals are important for studying the behavior of radium in the environment. Various instruments for measuring 226Ra are currently used: among the radiometric techniques that measure in bulk (no spatialization), there are gamma spectrometers and alpha spectrometers. Other instruments such as SEM-EDS can map the chemical elements thus providing information on the distribution of 226Ra, but are limited for ultra-trace analyses on natural geomaterials. Finally, autoradiography techniques can locate radioactivity, but are limited to the identification of the contribution of 226Ra when the 238U series is complete. This study focuses on spectroscopic autoradiography, a method for measuring both the energy of the alpha particle emissions and their positions on the autoradiograph. A gas detector based on a parallel ionization multiplier technology was used for this purpose. Alpha particle energy is dependent on the emitting radionuclides. In order to track the 226Ra, the energy spectrum of the 238U series was studied with modeling software. It appears possible to apply a thresholding on the energy spectrum to discriminate the 226Ra from the first alpha emitters of the 238U decay chain (i.e. 238U, 234U and 230Th, all below 5 MeV). The developed method was applied to a U-mill tailing sample prepared as a thin section. The sample was heterogeneous in terms of radioactivity and was not at secular equilibrium with 238U, as expected. The 226Ra was identified and localized, and different regions of interest were also analyzed with SEM-EDS elements cartography. This revealed 226Ra-rich barite (BaSO4) phases measured at 3 ppmRa on average and containing no uranium; and uranium in siderite (FeCO3), showing a strong 226Ra deficit compared with secular equilibrium. Spectroscopic autoradiography opens up possibilities for the analysis of heterogeneous geological samples containing natural alpha emitters such as 238U and 226Ra: the 226Ra can be localized and quantified at ultra-trace content, and the method developed can also identify newly (young) uranium phases by measuring 238U/226Ra activity disequilibrium.


Assuntos
Monitoramento de Radiação , Rádio (Elemento) , Urânio , Autorradiografia , Urânio/análise , Partículas alfa , Monitoramento de Radiação/métodos , Radioisótopos/análise , Rádio (Elemento)/análise
4.
Int J Mol Sci ; 25(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38203834

RESUMO

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes-Radium-223 and Radium-224 (223/224Ra)-in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting. To exploit the therapeutic gains of Ra across a wider spectrum of cancers, nanoparticles have recently been embraced as carriers to ensure the linkage of 223/224Ra to target-affine vectors. Exemplified by prior findings, Ra was successfully bound to several nano/microparticles, including lanthanum phosphate, nanozeolites, barium sulfate, hydroxyapatite, calcium carbonate, gypsum, celestine, or liposomes. Despite the lengthened tumor retention and the related improvement in the radiotherapeutic effect of 223/224Ra coupled to nanoparticles, the in vivo assessment of the radiolabeled nanoprobes is a prerequisite prior to clinical usage. For this purpose, experimental xenotransplant models of different cancers provide a well-suited scenario. Herein, we summarize the latest achievements with 223/224Ra-doped nanoparticles and related advances in targeted alpha radiotherapy.


Assuntos
Nanomedicina , Rádio (Elemento) , Rádio (Elemento)/uso terapêutico , Partículas alfa/uso terapêutico , Anticorpos Monoclonais
5.
J Radiat Res ; 65(1): 136-143, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38037422

RESUMO

We demonstrate the application of fluorescence optical fiber coupled to a telecom grade fiber as a sensor for alpha particles using alpha-specific ZnS(Ag) scintillation materials whose wavelength is down-shifted into a low-loss region of the telecom grade fiber transmission band. Telecom-grade fiber optics offer a solution for sensing alpha radiation in deep repositories and cask storage for radioactive materials due to the stability of SiO2 under normal environmental conditions and its relative radiation hardness at low radiation doses. Long-term nuclear waste storage facilities require sensors for the detection of leakage of radioactive materials that are maintenance-free, do not require power and can survive with no 'wear out' mechanisms for decades. By accomplishing the wavelength transformation, we maximize efficiencies in the detection of α-particles and signal transport and can detect alpha scintillation at distances on the order of >1 km with a sensor that is ~3% efficient and can be easily scaled as a sensor array. This paper describes the construction and testing of the sensor including manufacture of the controlled thickness films, verification of the wavelength shift from 450 to 620 nm and optimization of the sensitivity as a function of thickness. We also model the relative sensitivity of the film as a function of film thickness, and we demonstrate a signal-to-noise ratio of 10 at a range of greater than 1 km.


Assuntos
Partículas alfa , Fibras Ópticas , Dióxido de Silício , Tecnologia de Fibra Óptica
6.
Nucl Med Biol ; 126-127: 108387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37837782

RESUMO

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.


Assuntos
Astato , Humanos , Astato/uso terapêutico , Astato/química , Radioisótopos/química , Partículas alfa/uso terapêutico , Radioquímica/métodos
7.
Mol Imaging Biol ; 25(6): 991-1019, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845582

RESUMO

Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (α) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of α-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative "theranostic" platforms. Herein, the current landscape of α particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides are introduced and recent efforts towards their production for research and clinical use are described. The growing popularity of these radionuclides is explained through summarizing the biological effects of α radiation on cancer cells, which include DNA damage, activation of discrete cell death programs, and downstream immune responses. Examples of efficient α-theranostic design are described with an emphasis on strategies that lead to cellular internalization and the targeting of proteins involved in therapeutic resistance. Historical barriers to the clinical deployment of α-theranostic radiopharmaceuticals are also discussed. Recent progress towards addressing these challenges is presented along with examples of incorporating α-particle therapy in pharmaceutical platforms that can be easily converted into diagnostic counterparts.


Assuntos
Neoplasias , Compostos Radiofarmacêuticos , Compostos Radiofarmacêuticos/uso terapêutico , Partículas alfa/uso terapêutico , Radioisótopos/uso terapêutico , Preparações Farmacêuticas , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia
8.
Nucl Med Biol ; 126-127: 108389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37783103

RESUMO

INTRODUCTION: Four terbium isotopes 149,152,155,161Tb emitting various types of radiation can be used for both diagnostics and therapy. 152Tb emits positrons and is ideal for PET. 155Tb is considered a promising Auger emitter and a diagnostic pair for other terbium therapeutic isotopes. Several methods for the production of 155Tb using charged particle accelerators have been proposed, but they all have significant limitations. The restricted availability of this isotope hinders its medical applications. We have proposed a new method for production of 155Tb, irradiating enriched 155Gd by alpha particles. The possibility of simultaneous production of two isotopes of terbium, 152,155Tb, was also studied for more efficient cyclotron beam use. METHODS: Irradiation of 155Gd enriched targets and 155Gd / 151Eu tandem target with alpha-particles with an energy of 54 MeV was carried out at the U-150 cyclotron at the NRC "Kurchatov Institute". The cross sections of nuclear reactions on enr-155Gd were measured by the stack foil technique, detecting the gamma-radiation of the activation products. The separation of rare earth elements was performed by extraction chromatography with the LN Resin. 155Tb was produced via 155Dy decay. RESULTS: The cross sections for the 155,156Tb and 155,157Dy production were measured by the irradiation of a gadolinium target enriched with the 155Gd isotope with alpha-particles in an energy range of 54 → 33 MeV. The yield of 155Dy on a thick target at 54 MeV was 130 MBq/µAh, which makes it possible to obtain 1 GBq of 155Tb in 11 hour-irradiation with 20 µA beam current. The possibility of simultaneous production of 152,155Tb by irradiation of 155Gd and 151Eu tandem target with medium-energy alpha-particles is implemented. Optimal irradiation energy ranges of alpha -particles as 54 → 42 MeV for 155Tb and 42 → 34 MeV for 152Tb were suggested. Product activity and radionuclidic purity were calculated.


Assuntos
Partículas alfa , Térbio , Térbio/química , Partículas alfa/uso terapêutico , Radioisótopos/química , Elétrons
9.
Radiat Prot Dosimetry ; 199(15-16): 1926-1931, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819348

RESUMO

The aim of the study is to show a method of real-time determination of the dose deposited in a tissue-like medium by α-particles emitted from the 10B(n,α)7Li reaction. The applied research method is to determine the correlation between the measured density of α-particle traces and measured in real time the 478 keV prompt-gamma rays derived from the 10B(n,α)7Li reaction. To achieve this aim, an appropriate construction of an experimental set-up is needed. The experimental set-up built for the purpose of the measurements carried out in the MARIA Reactor at the National Centre for Nuclear Research in Swierk, Poland, is presented. The main challenges related to obtaining optimal conditions for the measurement of the 478 keV gamma photons; the preliminary results of spectrometric measurements and further studies are also discussed.


Assuntos
Partículas alfa , Terapia por Captura de Nêutron de Boro , Raios gama , Terapia por Captura de Nêutron de Boro/métodos , Radiometria/métodos , Análise Espectral
10.
Int J Mol Sci ; 24(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37686211

RESUMO

This paper presents an assessment of nuclear reaction yields of protons, α-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au, 11B, and 10B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible.


Assuntos
Nanopartículas , Neoplasias , Radiossensibilizantes , Humanos , Prótons , Neoplasias/radioterapia , Partículas alfa , Simulação por Computador , Radiossensibilizantes/uso terapêutico
11.
J Nucl Med ; 64(9): 1344-1351, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37591544

RESUMO

Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 "Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments" at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.


Assuntos
Elétrons , Compostos Radiofarmacêuticos , Compostos Radiofarmacêuticos/efeitos adversos , Partículas alfa/uso terapêutico , Meia-Vida , Agências Internacionais
12.
Radiat Prot Dosimetry ; 199(13): 1376-1383, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37394946

RESUMO

It is very important to evaluate the diameters (activity median aerodynamic diameter) of plutonium dioxide (PuO2) particles for internal exposure dose evaluation. In this study, a method of evaluating PuO2 particle diameters using an alpha-particle imaging detector was developed. PuO2 particles with different diameters were modeled by Monte Carlo simulation, and the change in the shape of the energy spectrum for each particle diameter was evaluated. Two different patterns were modeled, namely, the case of 239PuO2 and the case of PuO2 (including isotopic composition of Pu). Multiple regression analysis was performed to determine the PuO2 particle diameter from the obtained parameters. The simulated diameters and the diameters obtained with the regression model were in good agreement. The advantage of using the alpha-particle imaging detector is to measure the alpha energy spectrum for individual particle, and this allows accurate measurement of particle diameter distribution.


Assuntos
Diagnóstico por Imagem , Plutônio , Partículas alfa , Simulação por Computador , Método de Monte Carlo
13.
Phys Med ; 112: 102626, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37393861

RESUMO

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.


Assuntos
Braquiterapia , Humanos , Método de Monte Carlo , Dano ao DNA , Partículas alfa/uso terapêutico , DNA
14.
Sci Rep ; 13(1): 11198, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433844

RESUMO

There is agreement that high-LET radiation has a high Relative Biological Effectiveness (RBE) when delivered as a single treatment, but how it interacts with radiations of different qualities, such as X-rays, is less clear. We sought to clarify these effects by quantifying and modelling responses to X-ray and alpha particle combinations. Cells were exposed to X-rays, alpha particles, or combinations, with different doses and temporal separations. DNA damage was assessed by 53BP1 immunofluorescence, and radiosensitivity assessed using the clonogenic assay. Mechanistic models were then applied to understand trends in repair and survival. 53BP1 foci yields were significantly reduced in alpha particle exposures compared to X-rays, but these foci were slow to repair. Although alpha particles alone showed no inter-track interactions, substantial interactions were seen between X-rays and alpha particles. Mechanistic modelling suggested that sublethal damage (SLD) repair was independent of radiation quality, but that alpha particles generated substantially more sublethal damage than a similar dose of X-rays, [Formula: see text]. This high RBE may lead to unexpected synergies for combinations of different radiation qualities which must be taken into account in treatment design, and the rapid repair of this damage may impact on mechanistic modelling of radiation responses to high LETs.


Assuntos
Partículas alfa , Radiação Ionizante , Bioensaio , Dano ao DNA , Tolerância a Radiação
15.
Int J Mol Sci ; 24(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37511386

RESUMO

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.


Assuntos
Neoplasias da Próstata , Compostos Radiofarmacêuticos , Humanos , Masculino , Partículas alfa/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Compostos Radiofarmacêuticos/farmacologia , Ensaios Clínicos como Assunto
16.
PLoS One ; 18(6): e0286902, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37307266

RESUMO

DNA double strand breaks (DSBs) are a deleterious form of DNA damage. Densely ionising alpha radiation predominantly induces complex DSBs and sparsely ionising gamma radiation-simple DSBs. We have shown that alphas and gammas, when applied simultaneously, interact in producing a higher DNA damage response (DDR) than predicted by additivity. The mechanisms of the interaction remain obscure. The present study aimed at testing whether the sequence of exposure to alphas and gammas has an impact on the DDR, visualised by live NBS1-GFP (green fluorescent protein) focus dynamics in U2OS cells. Focus formation, decay, intensity and mobility were analysed up to 5 h post exposure. Focus frequencies directly after sequential alpha → gamma and gamma → alpha exposure were similar to gamma alone, but gamma → alpha foci quickly declined below the expected values. Focus intensities and areas following alpha alone and alpha → gamma were larger than after gamma alone and gamma → alpha. Focus movement was most strongly attenuated by alpha → gamma. Overall, sequential alpha → gamma exposure induced the strongest change in characteristics and dynamics of NBS1-GFP foci. Possible explanation is that activation of the DDR is stronger when alpha-induced DNA damage precedes gamma-induced DNA damage.


Assuntos
Partículas alfa , Registros , Raios gama , Quebras de DNA de Cadeia Dupla , Dano ao DNA , Proteínas de Fluorescência Verde
17.
Sci Rep ; 13(1): 9791, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328655

RESUMO

Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.


Assuntos
Radiação Cósmica , Prótons , Humanos , Partículas alfa/efeitos adversos , Radiação Cósmica/efeitos adversos , Radiação Ionizante , Mutação , Mutagênicos
18.
J Radiol Prot ; 43(3)2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37339608

RESUMO

A monitoring programme, in place since 2006, continues to recover radioactive particles (<2 mm diameter) and larger objects from the beaches of West Cumbria. The potential risks to members of the public using the beaches are mainly related to prolonged skin contact with or the inadvertent ingestion of small particles. Most particles are classified as either 'beta-rich' or 'alpha-rich' and are detected as a result of their caesium-137 or americium-241 content. Beta-rich particles generally also contain strontium-90, with90Sr:137Cs ratios of up to about 1:1, but typically <0.1:1. Alpha-rich particles contain plutonium isotopes, with Pu:241Amαratios usually around 0.5-0.6:1. 'Beta-rich' particles have the greatest potential to cause localised skin damage if held in stationary contact with the skin for prolonged periods. However, it is concluded that only particles of >106Bq of137Cs, with high90Sr:137Cs ratios, would pose a significant risk of causing acute skin ulceration. No particles of this level of activity have been found. Inadvertent ingestion of a particle will result in the absorption to blood of a small proportion of the radionuclide content of the particle. The subsequent retention of radionuclides in body organs and tissues presents a potential risk of the development of cancer. For 'beta-rich' particles with typical activities (mean 2 × 104Bq137Cs, Sr:Cs ratio of 0.1:1), the estimated committed effective doses are about 30µSv for adults and about 40µSv for 1 year old infants, with lower values for 'alpha-rich' particles of typical activities. The corresponding estimates of lifetime cancer incidence following ingestion for both particle types are of the order of 10-6for adults and up to 10-5for infants. These estimates are subject to substantial uncertainties but provide an indication of the low risks to members of the public.


Assuntos
Praias , Exposição Ambiental , Resíduos Radioativos , Poluentes Radioativos do Solo , Humanos , Lactente , Radioisótopos de Césio/efeitos adversos , Radioisótopos de Césio/análise , Plutônio/efeitos adversos , Plutônio/análise , Poluentes Radioativos do Solo/efeitos adversos , Poluentes Radioativos do Solo/análise , Reino Unido , Resíduos Radioativos/efeitos adversos , Resíduos Radioativos/análise , Adulto , Medição de Risco , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Pele/efeitos da radiação , Ingestão de Alimentos , Neoplasias/induzido quimicamente , Partículas beta/efeitos adversos , Partículas alfa/efeitos adversos
19.
Med Phys ; 50(8): 5176-5188, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37161766

RESUMO

BACKGROUND: Recent developments in alpha and beta emitting radionuclide therapy highlight the importance of developing efficient methods for patient-specific dosimetry. Traditional tabulated methods such as Medical Internal Radiation Dose (MIRD) estimate the dose at the organ level while more recent numerical methods based on Monte Carlo (MC) simulations are able to calculate dose at the voxel level. A precalculated MC (PMC) approach was developed in this work as an alternative to time-consuming fully simulated MC. Once the spatial distribution of alpha and beta emitters is determined using imaging and/or numerical methods, the PMC code can be used to achieve an accurate voxelized 3D distribution of the deposited energy without relying on full MC calculations. PURPOSE: To implement the PMC method to calculate energy deposited by alpha and beta particles emitted from the Ra-224 decay chain. METHODS: The GEANT4 (version 10.7) MC toolkit was used to generate databases of precalculated tracks to be integrated in the PMC code as well as to benchmark its output. In this regard, energy spectra of alpha and beta particles emitted by the Ra-224 decay chain were generated using GAMOS (version 6.2.0) and imported into GEANT4 macro files. Either alpha or beta emitting sources were defined at the center of a homogeneous phantom filled with various materials such as soft tissue, bone, and lung where particles were emitted either mono-directionally (for database generation) or isotropically (for benchmarking). Two heterogeneous phantoms were used to demonstrate PMC code compatibility with boundary crossing events. Each precalculated database was generated step-by-step by storing particle track information from GEANT4 simulations followed by its integration in a PMC code developed in MATLAB. For a user-defined number of histories, one of the tracks in a given database was selected randomly and rotated randomly to reflect an isotropic emission. Afterward, deposited energy was divided between voxels based on step length in each voxel using a ray-tracing approach. The radial distribution of deposited energy was benchmarked against fully simulated MC calculations using GEANT4. The effect of the GEANT4 parameter StepMax on the accuracy and speed of the code was also investigated. RESULTS: In the case of alpha decay, primary alpha particles show the highest contribution (>99%) in deposited energy compared to their secondary particles. In most cases, protons act as the main secondary particles in the deposition of energy. However, for a lung phantom, using a range cutoff parameter of 10 µm on primary alpha particles yields a higher contribution of secondary electrons than protons. Differences between deposited energy calculated by PMC and fully simulated MC are within 2% for all alpha and beta emitters in homogeneous and heterogeneous phantoms. Additionally, statistical uncertainties are less than 1% for voxels with doses higher than 5% of the maximum dose. Moreover, optimization of the parameter StepMax is necessary to achieve the best tradeoff between code accuracy and speed. CONCLUSIONS: The PMC code shows good performance for dose calculations deposited by alpha and beta emitters. As a stand-alone algorithm, it is suitable to be integrated into clinical treatment planning systems.


Assuntos
Algoritmos , Prótons , Humanos , Imagens de Fantasmas , Partículas alfa/uso terapêutico , Benchmarking
20.
Sci Rep ; 13(1): 7985, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198245

RESUMO

In search for critical elements, polymetallic nodules at the deep abyssal seafloor are targeted for mining operations. Nodules efficiently scavenge and retain several naturally occurring uranium-series radioisotopes, which predominantly emit alpha radiation during decay. Here, we present new data on the activity concentrations of thorium-230, radium-226, and protactinium-231, as well as on the release of radon-222 in and from nodules from the NE Pacific Ocean. In line with abundantly published data from historic studies, we demonstrate that the activity concentrations for several alpha emitters are often higher than 5 Bq g-1 at the surface of the nodules. These observed values can exceed current exemption levels by up to a factor of 1000, and even entire nodules commonly exceed these limits. Exemption levels are in place for naturally occurring radioactive materials (NORM) such as ores and slags, to protect the public and to ensure occupational health and radiation safety. In this context, we discuss three ways of radiation exposure from nodules, including the inhalation or ingestion of nodule fines, the inhalation of radon gas in enclosed spaces and the potential concentration of some radioisotopes during nodule processing. Seen in this light, inappropriate handling of polymetallic nodules poses serious health risks.


Assuntos
Monitoramento de Radiação , Urânio , Partículas alfa/efeitos adversos , Mineração , Radioisótopos/efeitos adversos , Oceano Pacífico , Urânio/efeitos adversos , Urânio/análise
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