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Applied Radiation and Isotopes :... Jul 2023We used Monte Carlo simulations to study release of Ra daughter nuclei from the seed used for Diffusing Alpha-Emitters Radiation Therapy (DART). Calculated desorption...
We used Monte Carlo simulations to study release of Ra daughter nuclei from the seed used for Diffusing Alpha-Emitters Radiation Therapy (DART). Calculated desorption probabilities for Po (15%) and Pb (12%) showed that they make a significant contribution to total release from the seed. We also showed that the dose to tissue from decays inside the 10 mm long seed exceeds 2.9 Gy for initial Ra activity of 3 μCi (111 kBq).
Topics: Alpha Particles; Brachytherapy; Computer Simulation; Monte Carlo Method
PubMed: 37099829
DOI: 10.1016/j.apradiso.2023.110825 -
Advanced Drug Delivery Reviews Sep 2008Alpha-particles are helium nuclei that deposit DNA damaging energy along their track that is 100 to 1000 times greater than that of conventionally used beta-particle... (Review)
Review
Alpha-particles are helium nuclei that deposit DNA damaging energy along their track that is 100 to 1000 times greater than that of conventionally used beta-particle emitting radionuclides for targeted therapy; the damage caused by alpha-particles is predominately double-stranded DNA breaks severe enough so as to be almost completely irreparable. This means that a small number of tracks through a cell nucleus can sterilize a cell and that, because the damage is largely irreparable, alpha-particle radiation is not susceptible to resistance as seen with external radiotherapy (e.g., in hypoxic tissue). The ability of a single track to influence biological outcome and the stochastic nature of alpha-particle decay require statistical or microdosimetric techniques to properly reflect likely biological outcome when the biologically relevant target is small or when a low number of radionuclide decays have occurred. In therapeutic implementations, microdosimetry is typically not required and the average absorbed dose over a target volume is typically calculated. Animal and cell culture studies have shown that, per unit absorbed dose, the acute biological effects of alpha-particles are 3 to 7 times greater than the damage caused by external beam or beta-particle radiation. Over the past ten to 15 years, alpha-particle emitting radionuclides have been investigated as a possible new class of radionuclides for targeted therapy. Results from the small number of clinical trials reported to date have shown efficacy without significant toxicity.
Topics: Alpha Particles; Animals; Clinical Trials as Topic; Humans; Neoplasms; Radiotherapy Dosage; Relative Biological Effectiveness
PubMed: 18541332
DOI: 10.1016/j.addr.2008.04.007 -
International Journal of Radiation... 2021High LET including alpha radiation-based approaches have been proved as a promising mode for cancer therapy owing to their biophysical and radiobiological advantages...
PURPOSE
High LET including alpha radiation-based approaches have been proved as a promising mode for cancer therapy owing to their biophysical and radiobiological advantages compared to photon beams. Studies pertaining to effect of α-radiation on cancer cells are limited to cytotoxic high doses.
MATERIALS AND METHODS
In this study, human lung adenocarcinoma (A549) cells were α-irradiated using Am α-irradiator and effects of low dose of alpha radiation on these cells was studied under and conditions.
RESULTS
Clonogenic and other assays showed increased cellular proliferation at lower doses (1.36 and 6.8 cGy) but killing at higher doses (13.6-54.4 cGy). Further studies at low dose of alpha (1.36 cGy) showed increased TGF-β1 in the conditioned medium (CM) at early time point (24 h) but CM replacement did not affect the clonogenic survival. In these cells, increased phosphorylation of connexin 43 was correlated with decrease in gap-junction communication observed by dye transfer co-culture experiment. A decrease in caveolin-1 but increase in survivin expression was observed in low dose α-irradiated cells. An increase in cyclinD1 and decrease in Bcl-2, the target proteins of survivin, was observed in these cells. Low dose α-irradiated cancer cells transplanted in SCID mice showed significantly higher tumor volume, which was accompanied with an increased fraction of mitotic and PCNA/Ki67 positive cells in these tumor tissues.
CONCLUSIONS
Taken together, our results suggest an increase in proliferation and tumor volume at and levels, respectively, when A549 cells were irradiated with low dose of α-radiation. These findings may be relevant for a better understanding of radiobiological processes during high LET-based cancer radiotherapy.
Topics: Alpha Particles; Animals; Caveolin 1; Cell Line, Tumor; Cell Proliferation; Connexin 43; Humans; Lung Neoplasms; Mice; Signal Transduction; Survivin
PubMed: 33416428
DOI: 10.1080/09553002.2021.1864044 -
Current Radiopharmaceuticals 2018Radiopharmaceutical therapy is a cancer treatment modality by which radiation is delivered directly to targeted tumor cells or to their microenvironment. This makes it... (Review)
Review
BACKGROUND
Radiopharmaceutical therapy is a cancer treatment modality by which radiation is delivered directly to targeted tumor cells or to their microenvironment. This makes it possible to deliver highly potent alpha-particle radiation. The short-range and highly potent nature of alpha-particles require a dosimetry methodology that considers microscale distributions of the alpha-emitting agent. The high energy deposition density along an alpha-particle track causes a spectrum of DNA lesions. The majority of these are irreparable DNA double-stranded breaks. Accordingly the biologic effects of alpha- particles are largely impervious to the adaptive and resistance mechanism that renders other therapeutics ineffectual.
OBJECTIVES
In this review, the radiobiology and dosimetry of alpha-particle emitting radionuclides as related to their use in radiopharmaceutical therapy, are presented.
CONCLUSION
Alpha-particle emitter radiopharmaceutical therapy is distinguished from other treatment modalities. Its safe clinical use requires an understanding of its unique dosimetry and radiobiology.
Topics: Alpha Particles; DNA Breaks, Double-Stranded; Humans; Neoplasms; Radiobiology; Radiochemistry; Radioimmunotherapy; Radioisotopes; Radiometry; Radiopharmaceuticals; Relative Biological Effectiveness
PubMed: 29697036
DOI: 10.2174/1874471011666180426130058 -
Journal of Labelled Compounds &... Sep 2019Targeted alpha therapy (TAT) is a promising approach for the treatment of cancer. The use of alpha emitters for cancer therapy has two distinct advantages over... (Review)
Review
Targeted alpha therapy (TAT) is a promising approach for the treatment of cancer. The use of alpha emitters for cancer therapy has two distinct advantages over conventional therapies. The short range of alpha radiation in human tissue (less than 0.1 mm), corresponding to only a few cell diameters, allows selective killing of targeted cancer cells while sparing surrounding healthy tissue. At the same time, the high energy (several MeV) of alpha radiation and its associated high linear energy transfer leads to highly effective cell kill. Consequently, alpha radiation can destroy cells which otherwise exhibit resistance to treatment with beta or gamma irradiation or chemotherapeutic drugs, and can thus offer a therapeutic option for tumors resistant to conventional therapies. Recent results demonstrating the remarkable therapeutic efficacy of alpha emitters to treat various cancers have underlined the clinical potential of TAT. This paper describes the recent clinical experience with Bi and Ac. In view of the enormous benefit of targeted cancer treatment with alpha emitters, their production will have to be considerably increased beyond current supply capabilities. Alternative production methods based on the irradiation of uranium, thorium, or radium targets at reactors or accelerator facilities have the potential to meet future demand.
Topics: Actinium; Alpha Particles; Bismuth; Humans; Radiochemistry; Radioisotopes; Radiotherapy
PubMed: 31369165
DOI: 10.1002/jlcr.3792 -
Annals of the ICRP Oct 2018Systemic or locoregionally administered alpha-particle emitters are highly potent therapeutic agents used in oncology that are fundamentally novel in their mechanism...
Systemic or locoregionally administered alpha-particle emitters are highly potent therapeutic agents used in oncology that are fundamentally novel in their mechanism and, most likely, overcome radiation resistance as the alpha particles emitted have a short range and a high linear energy transfer. The use of alpha emitters in a clinic environment requires extra measures with respect to imaging, dosimetry, and radiation protection. This is shown for the example of Ra dichloride therapy. After intravenous injection, Ra leaves the blood and is taken up rapidly in bone and bone metastases; it is mainly excreted via the intestinal tract. Ra can be imaged in patients with a gamma camera. Dosimetry shows that, after a series of six treatments for a 70-kg person with an overall administered activity of 23 MBq, Ra results in an absorbed alpha dose of approximately 17 Gy to the bone endosteum and approximately 1.7 Gy to the red bone marrow. During administration, special care must be taken to ensure that no spill is present on the skin of either the patient or staff. Due to the low dose rate, the treatment is normally performed on an outpatient basis; the patient and carers should receive written instructions about the therapy and radiation protection.
Topics: Alpha Particles; Humans; Radiation Protection; Radiometry; Radiotherapy; Radiotherapy, Image-Guided; Radium
PubMed: 29664326
DOI: 10.1177/0146645318756253 -
International Journal of Radiation... 2021Uncertainties regarding the magnitude of health effects following exposure to low doses of ionizing radiation remain a matter of concern both for professionals and for...
PURPOSE
Uncertainties regarding the magnitude of health effects following exposure to low doses of ionizing radiation remain a matter of concern both for professionals and for the public. There is consensus within the international radiation research community that more research is required on biological effects of radiation doses below 100 mGy applied at low dose rates. Moreover, there is a demand for increasing education and training of future radiation researchers and regulators. Research, education and training is primarily carried out at universities but university-based radiation research is often hampered by limited access to radiation sources. The aim of the present report is to describe small and cost-effective low activity gamma and alpha sources that can easily be installed and used in university laboratories.
METHODS AND RESULTS
A gamma radiation source was made from an euxenite-(Y) rock (Y,Ca,Ce,U,Th)(Nb,Ta,Ti)O) that was found in an abandoned mine in Sweden. It allows exposing cells grown in culture dishes to radiation at a dose rate of 50 Gy/h and lower. Three alpha sources were custom-made and yield a dose rate of 1 mGy/h each. The construction, dosimetry and cellular effects of the sources are described.
CONCLUSIONS
We hope that the report will stimulate research and training activities in the low dose field by facilitating access to radiation sources.
Topics: Alpha Particles; Gamma Rays; Radiation Dosage; Radiation Protection; Radiobiology; Uncertainty
PubMed: 33395328
DOI: 10.1080/09553002.2021.1867925 -
European Journal of Nuclear Medicine... Dec 2021The approval of RaCl for cancer therapy in 2013 has heralded a resurgence of interest in the development of α-particle emitting radiopharmaceuticals. In the last...
The approval of RaCl for cancer therapy in 2013 has heralded a resurgence of interest in the development of α-particle emitting radiopharmaceuticals. In the last decade, over a dozen α-emitting radiopharmaceuticals have entered clinical trials, spawned by strong preclinical studies. In this article, we explore the potential role of α-particle therapy in cancer treatment. We begin by providing a background for the basic principles of therapy with α-emitters, and we explore recent breakthroughs in therapy with α-emitting radionuclides, including conjugates with small molecules and antibodies. Finally, we discuss some outstanding challenges to the clinical adoption of α-therapies and potential strategies to address them.
Topics: Alpha Particles; Humans; Neoplasms; Radioisotopes; Radiopharmaceuticals
PubMed: 34175980
DOI: 10.1007/s00259-021-05431-y -
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 -
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