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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 -
Cells Jan 2021The delivery of radiation therapy (RT) for cancer with intent to cure has been optimized and standardized over the last 80 years. Both preclinical and clinical work... (Review)
Review
The Potentiation of Anti-Tumor Immunity by Tumor Abolition with Alpha Particles, Protons, or Carbon Ion Radiation and Its Enforcement by Combination with Immunoadjuvants or Inhibitors of Immune Suppressor Cells and Checkpoint Molecules.
The delivery of radiation therapy (RT) for cancer with intent to cure has been optimized and standardized over the last 80 years. Both preclinical and clinical work emphasized the observation that radiation destroys the tumor and exposes its components to the immune response in a mode that facilitates the induction of anti-tumor immunity or reinforces such a response. External beam photon radiation is the most prevalent in situ abolition treatment, and its use exposed the "abscopal effect". Particle radiotherapy (PRT), which has been in various stages of research and development for 70 years, is today available for the treatment of patients in the form of alpha particles, proton, or carbon ion radiotherapy. Charged particle radiotherapy is based on the acceleration of charged species, such as protons or carbon-12, which deposit their energy in the treated tumor and have a higher relative biological effectiveness compared with photon radiation. In this review, we will bring evidence that alpha particles, proton, or carbon ion radiation can destroy tumors and activate specific anti-tumor immune responses. Radiation may also directly affect the distribution and function of immune cells such as T cells, regulatory T cells, and mononuclear phagocytes. Tumor abolition by radiation can trigger an immune response against the tumor. However, abolition alone rarely induces effective anti-tumor immunity resulting in systemic tumor rejection. Immunotherapy can complement abolition to reinforce the anti-tumor immunity to better eradicate residual local and metastatic tumor cells. Various methods and agents such as immunoadjuvants, suppressor cell inhibitors, or checkpoint inhibitors were used to manipulate the immune response in combination with radiation. This review deals with the manifestations of particle-mediated radiotherapy and its correlation with immunotherapy of cancer.
Topics: Adjuvants, Immunologic; Alpha Particles; Heavy Ion Radiotherapy; Humans; Immune Checkpoint Inhibitors; Immunity; Neoplasms; Protons
PubMed: 33503958
DOI: 10.3390/cells10020228 -
Scientific Reports Jun 2023Ionizing 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...
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.
Topics: Humans; Protons; Alpha Particles; Cosmic Radiation; Radiation, Ionizing; Mutation; Mutagens
PubMed: 37328655
DOI: 10.1038/s41598-023-36845-3 -
Clinical Cancer Research : An Official... Feb 2013An α-particle, a (4)He nucleus, is exquisitely cytotoxic and indifferent to many limitations associated with conventional chemo- and radiotherapy. The exquisite... (Review)
Review
An α-particle, a (4)He nucleus, is exquisitely cytotoxic and indifferent to many limitations associated with conventional chemo- and radiotherapy. The exquisite cytotoxicity of α-radiation, the result of its high mean energy deposition [high linear energy transfer (LET)] and limited range in tissue, provides for a highly controlled therapeutic modality that can be targeted to selected malignant cells [targeted α-therapy (TAT)] with minimal normal tissue effects. A burgeoning interest in the development of TAT is buoyed by the increasing number of ongoing clinical trials worldwide. The short path length renders α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking, hematologic cancers, infections, and compartmental cancers such as ovarian cancer or neoplastic meningitis. Yet, despite decades of study of high LET radiation, the mechanistic pathways of the effects of this modality remain not well defined. The modality is effectively presumed to follow a simple therapeutic mechanism centered on catastrophic double-strand DNA breaks without full examination of the actual molecular pathways and targets that are activated that directly affect cell survival or death. This Molecular Pathways article provides an overview of the mechanisms and pathways that are involved in the response to and repair of TAT-induced DNA damage as currently understood. Finally, this article highlights the current state of clinical translation of TAT as well as other high-LET radionuclide radiation therapy using α-emitters such as (225)Ac, (211)At, (213)Bi, (212)Pb, and (223)Ra.
Topics: Alpha Particles; Clinical Trials as Topic; Humans; Neoplasms; Signal Transduction
PubMed: 23230321
DOI: 10.1158/1078-0432.CCR-12-0298 -
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 -
Journal of Environmental Radioactivity 2006The risk to non-human biota from exposure to ionizing radiation is of current international interest. In calculating radiation doses to humans, it is common to multiply... (Review)
Review
The risk to non-human biota from exposure to ionizing radiation is of current international interest. In calculating radiation doses to humans, it is common to multiply the absorbed dose by a factor to account for the relative biological effectiveness (RBE) of the radiation type. However, there is no international consensus on the appropriate value of such a factor for weighting doses to non-human biota. This paper summarizes our review of the literature on experimentally determined RBEs for internally deposited alpha-emitting radionuclides. The relevancy of each experimental result in selecting a radiation weighting factor for doses from alpha particles in biota was judged on the basis of criteria established a priori. We recommend a nominal alpha radiation weighting factor of 5 for population-relevant deterministic and stochastic endpoints, but to reflect the limitations in the experimental data, uncertainty ranges of 1-10 and 1-20 were selected for population-relevant deterministic and stochastic endpoints, respectively.
Topics: Alpha Particles; Animals; Animals, Laboratory; Biodiversity; Body Burden; Humans; International Cooperation; Radiation Dosage; Radiation Monitoring; Radiation Protection; Radiometry; Relative Biological Effectiveness; Safety
PubMed: 16377039
DOI: 10.1016/j.jenvrad.2005.10.009 -
Medical Physics Mar 2023Diffusing alpha-emitters Radiation Therapy ("DaRT") is a new method, presently in clinical trials, which allows treating solid tumors by alpha particles. DaRT relies on...
BACKGROUND
Diffusing alpha-emitters Radiation Therapy ("DaRT") is a new method, presently in clinical trials, which allows treating solid tumors by alpha particles. DaRT relies on interstitial seeds carrying μCi-level Ra activity below their surface, which release a chain of short-lived alpha emitters that spread throughout the tumor volume primarily by diffusion. Alpha dose calculations in DaRT are based on describing the transport of alpha emitting atoms, requiring new modeling techniques.
PURPOSE
A previous study introduced a simplified framework, the "Diffusion-Leakage (DL) model", for DaRT alpha dose calculations, and employed it to a point source, as a basic building block of arbitrary configurations of line sources. The aim of this work, which is divided into two parts, is to extend the model to realistic seed geometries (in Part I), and to employ single-seed calculations to study the properties of DaRT seed lattices (Part II). Such calculations can serve as a pragmatic guide for treatment planning in future clinical trials.
METHODS
We derive a closed-form asymptotic solution for an infinitely long cylindrical source, and extend it to an approximate time-dependent expression that assumes a uniform temporal profile at all radial distances from the source. We then develop a finite-element one-dimensional numerical scheme for a complete time-dependent solution of this geometry and validate it against the closed-form expressions. Finally, we discuss a two-dimensional axisymmetric scheme for a complete time-dependent solution for a seed of finite diameter and length. Different solutions are compared over the relevant parameter space, providing guidelines on their usability and limitations.
RESULTS
We show that approximating the seed as a finite line source comprised of point-like segments significantly underestimates the correct alpha dose, as predicted by the full two-dimensional calculation. The time-dependent one-dimensional solution is shown to coincide to sub-percent-level with the two-dimensional calculation in the seed midplane, and maintains an accuracy of a few percent up to ∼2 mm from the seed edge.
CONCLUSIONS
For actual treatment plans, the full two-dimensional solution should be used to generate dose lookup tables, similarly to the TG-43 format employed in conventional brachytherapy. Given the accuracy of the one-dimensional solution up to ∼2 mm from the seed edge it can be used for efficient parametric studies of DaRT seed lattices.
Topics: Humans; Brachytherapy; Neoplasms; Alpha Particles; Radiotherapy Dosage; Monte Carlo Method
PubMed: 36464914
DOI: 10.1002/mp.16145 -
Advanced Drug Delivery Reviews Jan 2017Radioimmunotherapy (RIT) aims to selectively deliver radionuclides emitting α-particles, β-particles or Auger electrons to tumors by conjugation to monoclonal... (Review)
Review
Radioimmunotherapy (RIT) aims to selectively deliver radionuclides emitting α-particles, β-particles or Auger electrons to tumors by conjugation to monoclonal antibodies (mAbs) that recognize tumor-associated antigens/receptors. The approach has been most successful for treatment of non-Hodgkin's B-cell lymphoma but challenges have been encountered in extending these promising results to the treatment of solid malignancies. These challenges include the low potency of β-particle emitters such as I, Lu or Y which have been commonly conjugated to the mAbs, due to their low linear energy transfer (LET=0.1-1.0keV/μm). Furthermore, since the β-particles have a 2-10mm range, there has been dose-limiting non-specific toxicity to hematopoietic stem cells in the bone marrow (BM) due to the cross-fire effect. Conjugation of mAbs to α-particle-emitters (e.g. Ac, Bi, Pb or At) or Auger electron-emitters (e.g. In, Ga, I or I) would increase the potency of RIT due to their high LET (50-230keV/μm and 4 to 26keV/μm, respectively). In addition, α-particles have a range in tissues of 28-100μm and Auger electrons are nanometer in range which greatly reduces or eliminates the cross-fire effect compared to β-particles, potentially reducing their non-specific toxicity to the BM. In this review, we describe the results of preclinical and clinical studies of RIT of cancer using radioimmunoconjugates emitting α-particles or Auger electrons, and discuss the potential of these high LET forms of radiation to improve the outcome of cancer patients.
Topics: Alpha Particles; Animals; Electrons; Humans; Immunoconjugates; Linear Energy Transfer; Neoplasms; Radioimmunotherapy; Radioisotopes
PubMed: 26705852
DOI: 10.1016/j.addr.2015.12.003 -
Current Radiopharmaceuticals Jul 2011With the increasing availability of alpha emitters, targeted α-particle therapy has emerged as a solution of choice to treat haematological cancers and micrometastatic... (Review)
Review
With the increasing availability of alpha emitters, targeted α-particle therapy has emerged as a solution of choice to treat haematological cancers and micrometastatic and minimal residual diseases. Alpha-particles are highly cytotoxic because of their high linear energy transfer (LET) and have a short range of a few cell diameters in tissue, assuring good treatment specificity. These radiologic features make conventional dosimetry less relevant for that context. Stochastic variations in the energy deposited in cell nuclei are important because of the microscopic target size, low number of α- particle traversals, and variation in LET along the α-particle track. Microdosimetry provides a conceptual framework that aims at a systematic analysis of the stochastic distribution of energy deposits in irradiated matter. The different quantities of microdosimetry and the different methods of microdosimetric calculations were described in the early eighties. Since then, numerous models have been published through the years and applied to analyse experimental data or to model realistic therapeutic situations. Major results have been an accurate description of the high toxicity of α-particles, and the description of the predominant effect of activity distribution at the cellular scale on toxicity or efficacy of potential targeted α-particle therapies. This last factor represents a major limitation to the use of microdosimetry in vivo because determination of the source - target distribution is complicated. The future contributions of microdosimetry in targeted α-particle therapy research will certainly depend on the ability to develop high-resolution detectors and on the implementation of pharmaco-kinetic models at the tumour microenvironment scale.
Topics: Alpha Particles; Dose-Response Relationship, Radiation; Humans; Monte Carlo Method; Neoplasms; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 22201713
DOI: 10.2174/1874471011104030266 -
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