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Scientific Reports May 2023In search for critical elements, polymetallic nodules at the deep abyssal seafloor are targeted for mining operations. Nodules efficiently scavenge and retain several...
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 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.
Topics: Alpha Particles; Mining; Radioisotopes; Pacific Ocean; Uranium; Radiation Monitoring
PubMed: 37198245
DOI: 10.1038/s41598-023-33971-w -
Radiation and Environmental Biophysics Mar 2020At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells.... (Review)
Review
At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there. In classical microdosimetry, the randomness of energy deposition in cellular sites is described by a stochastic quantity, the specific energy, which approximates the macroscopic dose for a sufficiently large number of energy deposition events. Typical examples of the alpha-emitting radionuclides in internal microdosimetry are radon progeny and plutonium in the lungs, plutonium and americium in bones, and radium in targeted radionuclide therapy. Several microdosimetric approaches have been proposed to relate specific energy distributions to radiobiological effects, such as hit-related concepts, LET and track length-based models, effect-specific interpretations of specific energy distributions, such as the dual radiation action theory or the hit-size effectiveness function, and finally track structure models. Since microdosimetry characterizes only the initial step of energy deposition, microdosimetric concepts are most successful in exposure situations where biological effects are dominated by energy deposition, but not by subsequently operating biological mechanisms. Indeed, the simulation of the combined action of physical and biological factors may eventually require the application of track structure models at the nanometer scale.
Topics: Alpha Particles; Animals; Bone and Bones; Humans; Lung; Radioisotopes; Radiometry
PubMed: 31863162
DOI: 10.1007/s00411-019-00826-w -
Cells May 2020Compact chromatin is linked to a poor tumour prognosis and resistance to radiotherapy from photons. We investigated DNA damage induction and repair in the context of...
Compact chromatin is linked to a poor tumour prognosis and resistance to radiotherapy from photons. We investigated DNA damage induction and repair in the context of chromatin structure for densely ionising alpha radiation as well as its therapeutic potential. Chromatin opening by histone deacetylase inhibitor trichostatin A (TSA) pretreatment reduced clonogenic survival and increased γH2AX foci in MDA-MB-231 cells, indicative of increased damage induction by free radicals using gamma radiation. In contrast, TSA pretreatment tended to improve survival after alpha radiation while γH2AX foci were similar or lower; therefore, an increased DNA repair is suggested due to increased access of repair proteins. MDA-MB-231 cells exposed to fractionated gamma radiation (2 Gy × 6) expressed high levels of stem cell markers, elevated heterochromatin H3K9me3 marker, and a trend towards reduced clonogenic survival in response to alpha radiation. There was a higher level of H3K9me3 at baseline, and the ratio of DNA damage induced by alpha vs. gamma radiation was higher in the aggressive MDA-MB-231 cells compared to hormone receptor-positive MCF7 cells. We demonstrate that heterochromatin structure and stemness properties are induced by fractionated radiation exposure. Gamma radiation-exposed cells may be targeted using alpha radiation, and we provide a mechanistic basis for the involvement of chromatin in these effects.
Topics: Acetylation; Alpha Particles; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Clone Cells; Female; Gamma Rays; Heterochromatin; Histones; Humans; Hydroxamic Acids; Lysine; Neoplastic Stem Cells; Radiation Exposure; Spheroids, Cellular
PubMed: 32397212
DOI: 10.3390/cells9051165 -
Nuclear Medicine and Biology Jan 2021Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic... (Review)
Review
Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic effects on tumor cells while mitigating dose to normal tissues. Two significant isotopes of interest within the area of TAT are thorium-227 and actinium-225 due to their nuclear characteristics. Both isotopes have physical half-lives suitable for coordination with larger biomolecules, and additionally actinium-225 has potential to serve as an in vivo generator. In this review, the authors will discuss the production, purification, labeling reactions, and biological studies of actinium-225 and thorium-227 complexes and clinical studies.
Topics: Alpha Particles; Animals; Humans; Isotope Labeling; Radiochemistry
PubMed: 33558017
DOI: 10.1016/j.nucmedbio.2020.08.004 -
Radiation and Environmental Biophysics Nov 2022Exosomes are spherical membrane nanovesicles secreted from cells, and they play an important role in tumor immune response, metastasis, angiogenesis, and survival....
Exosomes are spherical membrane nanovesicles secreted from cells, and they play an important role in tumor immune response, metastasis, angiogenesis, and survival. Studies investigating exosomes isolated from cells exposed to photon radiation commonly used in conventional radiotherapy demonstrate the influence of this type of radiation on exosome characteristics and secretion. There is currently no research investigating the effects of densely ionizing particles such as protons and alpha radiation on exosomes. Thus we have evaluated the cellular response of human prostate cancer cells exposed to 0, 2, and 6 Gy of alpha radiation emitted from the Am-241 source. Irradiated PC3 and DU145 cell lines, characterized by differences in radiosensitivity, were studied using apoptosis, LDH, and IL-6 assays. Additionally, the corresponding concentration and size of isolated exosomes were measured using NTA. We found that exposure to ionizing radiation resulted in gross changes in viability and cell damage. There were increased amounts of apoptotic or necrotic cells as a function of radiation dose. We demonstrated that irradiated PC3 cells secrete higher quantities of exosomes compared to DU145 cells. Additionally, we also found no statistical difference in exosome size for control and irradiated cells.
Topics: Male; Humans; Exosomes; Alpha Particles; PC-3 Cells; Radiation Tolerance; Cell Line, Tumor
PubMed: 36098819
DOI: 10.1007/s00411-022-00991-5 -
Frontiers in Medicine 2021Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of RaCl for patients with metastatic castration-resistant... (Review)
Review
Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of RaCl for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 μm) and their linear energy transfer (50-230 keV/μm), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited.
PubMed: 34386508
DOI: 10.3389/fmed.2021.692436 -
The Quarterly Journal of Nuclear... Mar 2023The use of alpha emitting radiotherapeutics is increasing, with further growth expected due to a number of clinical trials currently running involving new alpha...
The use of alpha emitting radiotherapeutics is increasing, with further growth expected due to a number of clinical trials currently running involving new alpha emitters. However, literature concerning radiation safety aspects of alpha emitting radionuclides is limited and most of the available literature concerns Ra. In general, the occupational exposure from alpha emitting radionuclides is expected to be low, as are doses to the public from external exposure. However, care must be taken to avoid skin contamination, inhalation, and ingestion. Not all alpha emitting radionuclides are identical, they often have very different associated decay chains and emissions. The decay chains and the manufacturing process should be carefully examined to identify any long-lived progeny or impurities. These may have an impact on the radiation safety processes required to limit occupational exposure and for waste management. Doses to the public must also be assessed, either arising directly from exposure to patients treated with radiotherapeutics, or via waste streams. Risk assessments should be in place when starting a new service covering all aspects of the preparation and administration, as well as any foreseeable incidents such as skin contamination or patient death, and the appropriate steps to take in these instances. It is imperative that with the increase in the use of alpha emitting radiotherapeutics more literature is published on radiation safety aspects, especially for new alpha emitting radiotherapeutics which often have very different characteristics than the currently established ones.
Topics: Humans; Radiation Protection; Radioisotopes; Risk Assessment; Alpha Particles; Radiation Dosage
PubMed: 36633588
DOI: 10.23736/S1824-4785.22.03501-4 -
Frontiers in Cell and Developmental... 2022Exposure to environmental ionizing radiation is prevalent, with greatest lifetime doses typically from high Linear Energy Transfer (high-LET) alpha particles the... (Review)
Review
Exposure to environmental ionizing radiation is prevalent, with greatest lifetime doses typically from high Linear Energy Transfer (high-LET) alpha particles the radioactive decay of radon gas in indoor air. Particle radiation is highly genotoxic, inducing DNA damage including oxidative base lesions and DNA double strand breaks. Due to the ionization density of high-LET radiation, the consequent damage is highly clustered wherein ≥2 distinct DNA lesions occur within 1-2 helical turns of one another. These multiply-damaged sites are difficult for eukaryotic cells to resolve either quickly or accurately, resulting in the persistence of DNA damage and/or the accumulation of mutations at a greater rate per absorbed dose, relative to lower LET radiation types. The proximity of the same and different types of DNA lesions to one another is challenging for DNA repair processes, with diverse pathways often confounding or interplaying with one another in complex ways. In this context, understanding the state of the higher order chromatin compaction and arrangements is essential, as it influences the density of damage produced by high-LET radiation and regulates the recruitment and activity of DNA repair factors. This review will summarize the latest research exploring the processes by which clustered DNA damage sites are induced, detected, and repaired in the context of chromatin.
PubMed: 35912116
DOI: 10.3389/fcell.2022.910440 -
Journal of Medical Imaging and... Dec 2019Despite ongoing efforts with new chemotherapeutics, small-molecule inhibitors and biologics, patients with distant metastases continue to have a grim prognosis.... (Review)
Review
Despite ongoing efforts with new chemotherapeutics, small-molecule inhibitors and biologics, patients with distant metastases continue to have a grim prognosis. Radiopharmaceutical therapy (RPT) with alpha-particle-emitting radionuclides has shown efficacy against widespread disease. Alpha-particle emitters are particularly effective because their short range and high energy deposit density lead to complex and largely irreparable DNA double-strand breaks. The high potency against tumors can also lead to high toxicity. Unlike most systemic treatment of cancer, the biodistribution of RPT agents may be imaged in humans using nuclear medicine imaging modalities. In this context, dosimetry provides a precision medicine approach to implementing RPT with alpha-emitters.
Topics: Alpha Particles; Humans; Neoplasms; Radiation Injuries; Radiometry; Radiopharmaceuticals; Radiotherapy; Radiotherapy Dosage
PubMed: 31537496
DOI: 10.1016/j.jmir.2019.07.007 -
Seminars in Nuclear Medicine Mar 2020Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms, arising from cells of the endocrine system, with various clinical behaviors. Although these neoplasms... (Review)
Review
Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms, arising from cells of the endocrine system, with various clinical behaviors. Although these neoplasms are considered rare, a significant increase in the incidence and detectability of NET has been noted in many epidemiological studies in recent years. Among the various therapeutic options, peptide receptor radionuclide therapy (PRRT), using somatostatine has been shown to be highly effective and a well-tolerated therapy, improving survival parameters. The current use of radionuclides for PRRT is β-emitters. Due to hypoxia cancer tissue could be resistant for β-emitters. Quite long penetration range had a significant impact on side effects. α-particles with higher energy and shorter penetration range in comparison to β-particles, have distinct advantages for use in targeted therapy. The clinical experience with somatostatine based targeted α therapy (TAT) in NET showed very promising results even in patienicts refractory to treatment with β-emitters. This article summarizes current developments in preclinical and clinical investigation on TAT in NET.
Topics: Alpha Particles; Animals; Clinical Trials as Topic; Humans; Molecular Targeted Therapy; Neuroendocrine Tumors; Treatment Outcome
PubMed: 32172802
DOI: 10.1053/j.semnuclmed.2019.11.003