-
Applied Radiation and Isotopes :... Jan 2012This paper addresses an approach to the theory and practice of electrodeposition processes of alpha-emitting nuclides. Some of the main contributions made to this field... (Review)
Review
This paper addresses an approach to the theory and practice of electrodeposition processes of alpha-emitting nuclides. Some of the main contributions made to this field are reviewed, including the rotating disk electrode technique. Also, several interpretations concerning the electrodeposition process as well as a number of practical recommendations are included in the study.
Topics: Alpha Particles; Electroplating; Equipment Design; Radioisotopes; Radionuclide Generators
PubMed: 21975108
DOI: 10.1016/j.apradiso.2011.09.010 -
Journal of Medical Imaging and... Dec 2019Radiolabeled antibodies allow for selective targeting of the cancer cells within a tumor. Both beta- and alpha-emitting radioisotopes can be linked to the antibodies for... (Review)
Review
Radiolabeled antibodies allow for selective targeting of the cancer cells within a tumor. Both beta- and alpha-emitting radioisotopes can be linked to the antibodies for delivery of radiation to the cells. The choice of the radionuclide would depend on the biological characteristics of the antibody including its biodistribution and biological half-life. Alpha-emitting isotopes deliver high energy to target sites within short range and therefore less radiation to adjacent normal tissues. Whole antibodies have long biological clearance times that may be limiting due to radiation levels to blood and marrow. Novel strategies, such as development of smaller antibody fragments such as minibodies and diabodies, which have faster biological clearance, engineered bispecific antibodies, and multistep targeting that uses pretargeting and bioorthogonal click chemistry methods, appear promising. Several novel targets are being investigated in early-phase studies. This review provides a brief summary and current status of radioimmunotargeted agents in oncology.
Topics: Alpha Particles; Humans; Neoplasms; Radioimmunotherapy; Radiometry; Radiotherapy; Theranostic Nanomedicine
PubMed: 31451417
DOI: 10.1016/j.jmir.2019.07.006 -
Seminars in Nuclear Medicine Mar 2020The short range and high linear energy transfer of α-particles offer the potential for efficient tumor killing while sparing normal bystander cells. Hematologic... (Review)
Review
The short range and high linear energy transfer of α-particles offer the potential for efficient tumor killing while sparing normal bystander cells. Hematologic malignancies are ideally suited to targeted α-particle therapy (TAT) due to easy accessibility of malignant cells in blood, bone marrow, lymph nodes, and spleen as well as their radiosensitivity. Most clinical trials using α-particle therapy for hematologic malignancies have focused on acute myeloid leukemia (AML); however, preclinical studies have shown activity against other diseases such as non-Hodgkin's lymphoma and multiple myeloma. To date, the short-lived radionuclide bismuth-213 (Bi) and its parent actinium-225 (Ac) have been used clinically, but trials with astatinie-211 (At) have recently begun, and thorium-227 (Th) has shown promising preclinical results. Lintuzumab is a humanized monoclonal antibody that targets the cell surface antigen CD33, which is expressed on the vast majority of AML cells. Initial studies showed that Bi-labeled lintuzumab had antileukemic activity and could produce remissions after partial cytoreduction with cytarabine. An initial phase I trial demonstrated that a single infusion of Ac-lintuzumab could be given safely at doses upto 111 kBq/kg with antileukemic activity across all dose levels. A second phase I study showed that fractionated-dose Ac-lintuzumab could be safely combined with low-dose cytarabine and produced objective responses in 28% of older patients with untreated AML. In a phase II study, treatment with Ac-lintuzumab monotherapy for a similar patient population resulted in remission in 69% of patients receiving two fractions of 74 kBq/kg and 22% of patients receiving two 55.5-kBq/kg fractions. Additionally, TAT may be useful in intensifying antileukemic therapy prior to hematopoietic cell transplantation, and pretargeting strategies offer the possibility for improved tumor-to-normal organ dose ratios.
Topics: Alpha Particles; Clinical Trials as Topic; Hematologic Neoplasms; Humans; Molecular Targeted Therapy; Safety
PubMed: 32172800
DOI: 10.1053/j.semnuclmed.2019.09.002 -
Radiation Oncology (London, England) Jun 2018While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative...
BACKGROUND
While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues.
METHODS
Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival.
RESULTS
The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (< 5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 - 51%).
CONCLUSIONS
The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.
Topics: Alpha Particles; Cell Line, Tumor; Cell Nucleus; Cell Survival; Cytoplasm; Humans; Imaging, Three-Dimensional; Radiometry; Relative Biological Effectiveness; Reproducibility of Results; Spheroids, Cellular
PubMed: 29880059
DOI: 10.1186/s13014-018-1034-x -
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 -
Journal of Nuclear Medicine : Official... Jul 2018The use of radioactive sources to deliver cytotoxic ionizing radiation to disease sites dates back to the early 20th century, with the discovery of radium and its... (Review)
Review
The use of radioactive sources to deliver cytotoxic ionizing radiation to disease sites dates back to the early 20th century, with the discovery of radium and its physiologic effects. α-emitters are of particular interest in the field of clinical oncology for radiotherapy applications. The first part of this review explored the basic radiochemistry, high cell-killing potency, and availability of α-emitting radionuclides, together with hurdles such as radiolabeling methods and daughter redistribution. The second part of this review will give an overview of the most promising and current uses of α-emitters in preclinical and clinical studies.
Topics: Alpha Particles; Animals; Beta Particles; Humans; Radiochemistry; Translational Research, Biomedical
PubMed: 29496984
DOI: 10.2967/jnumed.117.204651 -
Medecine Sciences : M/S Apr 2016Alpha-radioimmunotherapy (α-RIT) is a targeted anti-tumor therapy using usually a monoclonal antibody specific for a tumor antigen that is coupled to an α-particle... (Review)
Review
Alpha-radioimmunotherapy (α-RIT) is a targeted anti-tumor therapy using usually a monoclonal antibody specific for a tumor antigen that is coupled to an α-particle emitter. α-emitters represent an ideal tool to eradicate disseminated tumors or metastases. Recent data demonstrate that ionizing radiation in addition to its direct cytotoxic ability can also induce an efficient anti-tumor immunity. This suggests that biologic effects on irradiated tissues could be used to potentiate immunotherapy efficacy and opens the way for development of new therapies combining α-RIT and different types of immunotherapy.
Topics: Alpha Particles; Animals; Humans; Immune System; Neoplasms; Radioimmunotherapy
PubMed: 27137693
DOI: 10.1051/medsci/20163204014 -
Journal of Nuclear Medicine : Official... Jun 2018With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous... (Review)
Review
With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters.
Topics: Alpha Particles; Humans; Isotope Labeling; Radiochemistry
PubMed: 29545378
DOI: 10.2967/jnumed.116.186338 -
European Journal of Nuclear Medicine Sep 1998This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of... (Review)
Review
This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of astatine-211, bismuth-212, lead-212, actinium-225, bismuth-213, fermium-255, radium-223 and terbium-149, which at present are the most promising alpha-emitting isotopes available for human clinical use. The selective cytotoxicity offered by alpha particle-emitting radioimmunoconstructs is due to the high linear energy transfer and short particle path length of these radionuclides. Based upon the pharmacokinetics of alpha particle-emitting radioimmunoconstructs, both stochastic and conventional dosimetric methodology is discussed, as is the preclinical and initial clinical use of these radionuclides conjugated to monoclonal antibodies for the treatment of human neoplasia.
Topics: Alpha Particles; Animals; Humans; Radioimmunotherapy; Radioisotopes; Radiotherapy Dosage
PubMed: 9724387
DOI: 10.1007/s002590050306 -
International Journal of Radiation... 2022Radium is the most common source of alpha radiation exposure to humans and non-human species in the environment but the dosimetry is complicated by the decay chain which...
PURPOSE
Radium is the most common source of alpha radiation exposure to humans and non-human species in the environment but the dosimetry is complicated by the decay chain which involves gamma exposure due to radon daughters. This paper seeks to determine the separate contributions of alpha and gamma doses to the total dose and total direct and non-targeted effect in a fish and a human cell line.
MATERIALS AND METHODS
This study aimed to isolate the effect of alpha particles following exposure to low doses of radium in cells, and their progeny which received no further exposure. This was initially done by comparing the survival values of a human keratinocyte cell line (HaCaT) and an embryonic Chinook salmon cell line (CHSE-214) exposed to gamma radiation, from survival of the same cell lines exposed to mixed alpha and gamma radiation through exposure to Ra-226 and its decay products. A Monte Carlo simulation was later performed to determine the contributions of radium decay products including radon daughters.
RESULTS
The human cell line showed increased radioresistance when exposed to low doses of alpha particles. In contrast the fish cell line, which demonstrated radioresistance to low dose gamma radiation, showed increased lethality when exposed to low doses of alpha particles. Significant and complex levels of non-targeted effects were induced in progeny of irradiated cells. The simulation showed that gamma and beta decay products did not contribute significant dose and the highest beta dose was below the threshold for inducing non-targeted effects.
CONCLUSIONS
The results confirm the need to consider the dose-response relationship when developing radiation weighting factors for low dose exposures, as well as the need to be aware of possible cell line and species differences.
Topics: Alpha Particles; Animals; Radiation Exposure; Radiometry; Radium; Radon; Radon Daughters
PubMed: 33332185
DOI: 10.1080/09553002.2020.1866226