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Genetics and Molecular Research : GMR Nov 2014Alpha (α)-particle radiation has been thoroughly studied in the occupational and residential environments, but biological mechanisms induced by α-particle radiation on...
Alpha (α)-particle radiation has been thoroughly studied in the occupational and residential environments, but biological mechanisms induced by α-particle radiation on plants are not clearly understood. In this study, radiation effects were examined using different total doses (1, 10, 100 Gy, respectively) of 241Am, α-particle on Arabidopsis embryos. No significant difference in the germination percentage was observed between the 3 levels of doses and the control. Germination speed and root length were increased by treatment with the 1-Gy dose of a-particles, and decreased by treatment with 10- and 100-Gy doses. Moreover, the bending degree of roots increased with radiation dose, and the roots showed an "S" shape when treated with the 100-Gy dose. Root bending under the 100-Gy dose was inhibited by scavengers of reactive oxygen species (ROS). Root gravitropism and root length may respond to the consistency of ROS induced by irradiation. Further analysis of the physiological effects revealed that an increase in a-particle radiation intensity enhanced the activity of catalase and the content of malondialdehyde, but superoxide dismutase activity was reduced by treatment with 100-Gy radiation of a-particles, suggesting that the high linear energy transfer of a-particles may cause a relatively high level of membrane lipid preoxidation and high accumulation of ROS. ROS showed both physiological and morphological responses following exposure to α-particle radiation in Arabidopsis embryos.
Topics: Alpha Particles; Antioxidants; Arabidopsis; Catalase; Germination; Gravitropism; Lipid Peroxidation; Malondialdehyde; Meristem; Plant Roots; Reactive Oxygen Species; Seedlings; Seeds; Superoxide Dismutase
PubMed: 25501166
DOI: 10.4238/2014.November.12.5 -
Seminars in Nuclear Medicine Mar 2020As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the... (Review)
Review
As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
Topics: Alpha Particles; Humans; Radiobiology; Radiometry; Radiopharmaceuticals
PubMed: 32172797
DOI: 10.1053/j.semnuclmed.2019.11.002 -
Journal of Nuclear Medicine : Official... Jan 2005The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies.... (Review)
Review
The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies. Since the alpha- and beta-particles emitted during the decay of radioisotopes differ in significant ways, proper selection of isotope and antibody combinations is crucial to making radioimmunotherapy a standard therapeutic modality. Because of the short pathlength (50-80 microm) and high linear energy transfer ( approximately 100 keV/microm) of alpha-emitting radioisotopes, targeted alpha-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissues than beta-emitters. These properties make targeted alpha-particle therapy ideal for the elimination of minimal residual or micrometastatic disease. Radioimmunotherapy using alpha-emitters such as (213)Bi, (211)At, and (225)Ac has shown activity in several in vitro and in vivo experimental models. Clinical trials have demonstrated the safety, feasibility, and activity of targeted alpha-particle therapy in the treatment of small-volume and cytoreduced disease. Further advances will require investigation of more potent isotopes, new sources and methods of isotope production, improved chelation techniques, better methods for pharmacokinetic and dosimetric modeling, and new methods of isotope delivery such as pretargeting. Treatment of patients with less-advanced disease and, ultimately, randomized trials comparing targeted alpha-particle therapy with standard approaches will be required to determine the clinical utility of this approach.
Topics: Alpha Particles; Animals; Antibodies, Monoclonal; Clinical Trials as Topic; Drug Delivery Systems; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15653670
DOI: No ID Found -
Annals of Oncology : Official Journal... Nov 2019Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor... (Review)
Review
Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.
Topics: Actinium; Alpha Particles; Clinical Trials, Phase III as Topic; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Precision Medicine; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunotherapy; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Tumor Microenvironment
PubMed: 31418764
DOI: 10.1093/annonc/mdz270 -
Current Radiopharmaceuticals Oct 2011Alpha particle-emitting isotopes are being investigated in radioimmunotherapeutic applications because of their unparalleled cytotoxicity when targeted to cancer and... (Review)
Review
Alpha particle-emitting isotopes are being investigated in radioimmunotherapeutic applications because of their unparalleled cytotoxicity when targeted to cancer and their relative lack of toxicity towards untargeted normal tissue. Actinium- 225 has been developed into potent targeting drug constructs and is in clinical use against acute myelogenous leukemia. The key properties of the alpha particles generated by 225Ac are the following: i) limited range in tissue of a few cell diameters; ii) high linear energy transfer leading to dense radiation damage along each alpha track; iii) a 10 day halflife; and iv) four net alpha particles emitted per decay. Targeting 225Ac-drug constructs have potential in the treatment of cancer.
Topics: Actinium; Alpha Particles; Animals; Antibodies, Monoclonal; Clinical Trials as Topic; Humans; Liposomes; Models, Animal; Neoplasms; Radioimmunotherapy; Radiopharmaceuticals; Radiotherapy Dosage
PubMed: 22202153
DOI: 10.2174/1874471011104040306 -
Oncology Reviews 2022Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes... (Review)
Review
Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes through which people are exposed to radon and its decay products. During the inhalation of these radioactive aerosols, deposition takes place in different regions of the human respiratory tract. The deposited aerosols carrying radon and its progeny undergo a continuous radioactive transformation and expose the lung to ionizing alpha radiation, which can destroy the sensitive cells in the lung, causing a mutation that turns cancerous. Radon which is a colorless, odorless, and tasteless radioactive noble gas is a major health concern and is the second leading cause of lung cancer. To address this, an indoor radon survey was conducted in many countries internationally, with results showing that indoor radon concentration has a seasonal variation. This is due to the fluctuation of environmental parameters and the geological nature of buildings. Its concentration was found to be maximum in the cool (winter) season and a minimum concentration was recorded in the warm (summer) season of the year.
PubMed: 36531161
DOI: 10.3389/or.2022.10570 -
Journal of Nuclear Medicine : Official... Oct 2022Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety...
Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. In this study, we investigated the consequences of Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Ra accumulated in bones and induced zonal radiation damage confined to the bone interface, followed by replacement of the impaired areas with adipocyte infiltration, as monitored by 3-dimensional multiphoton microscopy ex vivo. Flow cytometry and single-cell transcriptomic analyses on bone marrow hematopoietic populations revealed transient, nonspecific Ra-mediated cytotoxicity on resident populations, including stem, progenitor, and mature leukocytes. This toxicity was paralleled by a significant decrease in white blood cells and platelets in peripheral blood-an effect that was overcome within 40 d after treatment. Ra exposure did not impair full hematopoietic reconstitution, suggesting that bone marrow function is not permanently hampered. Our results provide a comprehensive explanation of Ra reversible effects on bone marrow cells and exclude long-term myelotoxicity, supporting safety for patients.
Topics: Alpha Particles; Bone Marrow; Bone and Bones; Flow Cytometry; Humans; Male; Radioisotopes
PubMed: 35177425
DOI: 10.2967/jnumed.121.263310 -
Proceedings of the National Academy of... Sep 2002Low doses of alpha radiation in basements have been causally implicated in lung cancer. Previous studies have concentrated on high dose effects, for which no significant...
Low doses of alpha radiation in basements have been causally implicated in lung cancer. Previous studies have concentrated on high dose effects, for which no significant repair was found. In the present study, the methodology for measuring mutation by quantitating mitotic breaks and gaps was found to be applicable to G2-phase Chinese hamster ovary cells irradiated with 10-50 cGy of alpha radiation. The mutation yield in such cells closely resembles that of gamma irradiation. Caffeine, which inhibits repair, produces the same straight line increase of alpha and gamma mutation yields plotted against the dose. In the absence of caffeine, the repair of alpha radiation lesions is almost twice as great as for gamma radiation. Mitotic index changes substantiate these interpretations. It is proposed that the higher ion density associated with alpha radiation may result in fewer lesions being missed by the repair processes. The quantitation of chromosomal lesions for G2 cells exposed to low doses of alpha radiation, gamma radiation, or chemical mutagens in the presence and absence of caffeine is a rapid and reproducible methodology. Protection from mutational disease in a fashion similar to the use of sanitation for infectious disease appears practical.
Topics: Alpha Particles; Animals; CHO Cells; Chromosome Aberrations; Cricetinae; DNA Repair; G2 Phase; Gamma Rays; Humans; Lung Neoplasms; Mitotic Index; Mutagenesis; Neoplasms, Radiation-Induced; Radiation Dosage; Radiation Tolerance
PubMed: 12198179
DOI: 10.1073/pnas.152433699 -
Molecules (Basel, Switzerland) Apr 2021Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after... (Review)
Review
Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (RaCl), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.
Topics: Alpha Particles; Bone Neoplasms; Humans; Ligands; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 33918705
DOI: 10.3390/molecules26082162 -
The Quarterly Journal of Nuclear... Dec 2004An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides... (Review)
Review
An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.
Topics: Actinium; Alpha Particles; Antibodies, Monoclonal; Astatine; Bismuth; Humans; Isotopes; Neoplasms; Practice Patterns, Physicians'; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640792
DOI: No ID Found