Alpha-emitting Radionuclides Research Articles

Tumor immunotargeting using innovative radionuclides.

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

Sample pretreatment in the determination of specific alpha emitters in drinking water using [Ba+Fe]-coprecipitation method

The [Ba+Fe]-coprecipitation method is applied to measure gross alpha activity for radiological examination of drinking water in the laboratory. This method collects all the alpha-emitting radionuclides of interest (natural alpha emitters and transuranium elements) in a precipitate on a filter. This paper describes an investigation of sample pretreatment of the precipitate collected by the [Ba+Fe]-coprecipitation method for gross alpha activity determination. The aim of this preliminary work is to be a starting point to develop simple and rapid radiochemical procedures for specific alpha emitters (polonium, radium, thorium, uranium, plutonium and americium), in contrast to the sophisticated, expensive and time-consuming alpha spectrometry method. The sample pretreatment aspects considered include quantitative [Ba+Fe]-coprecipitation, two methods for precipitate treatment (leaching and complete destruction of the filter), and the determination of the alpha-emitting proportions present in the barium sulfate precipitate and acid solution obtained after precipitate treatment. Furthermore, a radiochemical procedure for 226Ra determination was performed and finally, the sample pretreatment proposed in this work was summarized.

Targeted alpha anticancer therapies: update and future prospects.

Targeted alpha therapy (TAT) is an emerging option for local and systemic cancer treatment. Preclinical research and clinical trials show that alpha-emitting radionuclides can kill targeted cancer cells while sparing normal cells, thus reducing toxicity. 223RaCl2 (Xofigo®) is the first alpha emitting radioisotope to gain registration in the US for palliative therapy of prostate cancer bone metastases by indirect physiological targeting. The alpha emitting radioisotopes 211At, 213Bi, 225Ac and 227Th are being used to label targeting vectors such as monoclonal antibodies for specific cancer therapy indications. In this review, safety and tolerance aspects are considered with respect to microdosimetry, specific energy, Monte Carlo model calculations, biodosimetry, equivalent dose and mutagenesis. The clinical efficacy of TAT for solid tumors may also be enhanced by its capacity for tumor anti-vascular (TAVAT) effects. This review emphasizes key aspects of TAT research with respect to the PAI2-uPAR complex and the monoclonal antibodies bevacizumab, C595 and J591. Clinical trial outcomes are reviewed for neuroendocrine tumors, leukemia, glioma, melanoma, non-Hodgkins lymphoma, and prostate bone metastases. Recommendations and future directions are proposed.

Nano-cerium vanadate: A novel inorganic ion exchanger for removal of americium and uranium from simulated aqueous nuclear waste

Cerium vanadate nanopowders were synthesized by a facile low temperature co-precipitation method. The product was characterized by X-ray diffraction and transmission electron microscopy and found to consist of ∼25nm spherical nanoparticles. The efficiency of these nanopowders for uptake of alpha-emitting radionuclides 233U (4.82MeV α) and 241Am (5.49MeV α, 60keV γ) has been investigated. Thermodynamically and kinetically favorable uptake of these radionuclides resulted in their complete removal within 3h from aqueous acidic feed solutions. The uptake capacity was observed to increase with increase in pH as the zeta potential value decreased with the increase in pH but effect of ionic strength was insignificant. Little influence of the ions like Sr2+, Ru3+, Fe3+, etc., in the uptake process indicated CeVO4 nanopowders to be amenable for practical applications. The isotherms indicated predominant uptake of the radioactive metal ions in the solid phase of the exchanger at lower feed concentrations and linear Kielland plots with positive slopes indicated favorable exchange of the metal ions with the nanopowder. Performance comparison with the other sorbents reported indicated excellent potential of nano-cerium vanadate for removing americium and uranium from large volumes of aqueous acidic solutions.

Combined drug and surgery treatment of plutonium-contaminated wounds: indications obtained using a rodent model.

There is an important requirement following accidental actinide contamination of wounds to limit the dissemination and retention of such alpha-emitting radionuclides. To reduce wound and systemic contamination, treatment approaches include chelation therapy with or without wound excision. However, it has been hypothesized that wound excision could lead to increased contaminant release and systemic organ retention. This study in the rat addresses this question. Anesthetized rats were contaminated with plutonium nitrate following wounding by deep incision of hind leg muscle. Excision of tissue at the contaminated site was performed 7 d later with or without Diethylene Triamine Pentaacetic Acid (DTPA) treatment (30 μmol kg⁻¹ i.v.). Pu urinary excretion was then measured for a further 3 d, and animals were euthanized at 14 d after contamination. Tissue samples were evaluated for Pu activity and histology. At 7 d after contamination, around 50% of the initial activity remained at the wound site. An average of 16% of this activity was then removed by surgery. Surgery alone resulted in increased urinary excretion, suggesting release from the wound site, but no subsequent increases in organ retention (bone, liver) were observed at 14 d. Indeed, organ Pu activity was slightly reduced. The combination of surgery and DTPA or DTPA treatment alone was much more effective than excision alone as shown by the markedly increased urinary Pu excretion and decreased tissue levels. This is the first report in an experimental rodent model of resection of Pu-contaminated wound. Urinary excretion data provide evidence for the release of activity as a result of surgery, but this does not appear to lead to further Pu organ retention. However, a combination of prior DTPA treatment with wound excision is particularly effective.

Radon in private drinking water wells

At least 10% of inhabitants in the Czech Republic are supplied with water from private sources (private wells, boreholes). With the increasing cost of water, the number of people using their own sources of drinking water will be likely to increase. According to the Decree of the State Office for Nuclear Safety about the Radiation Protection 307/2002 as amended by Decree 499/2005, the guideline limit for the supplied drinking water ('drinking water for public supply') for radon concentration is 50 Bq·l(-1). This guideline does not apply to private sources of drinking water. Radon in water influences human health by ingestion and also by inhalation when radon is released from water during showering and cooking. This paper presents results of measurements of radon concentrations in water from private wells in more than 300 cases. The gross concentration of alpha-emitting radionuclides and the concentrations of radium and uranium were also determined.

An analytical model for calculating internal dose conversion coefficients for non-human biota

To assess the radiation burden of non-human living organisms, dose coefficients are available in the literature, precalculated by assuming an ellipsoidal shape of each organism. A previously developed analytical method was applied for the determination of absorbed fractions inside ellipsoidal volumes from alpha, beta, and gamma radiations to the calculation of dose conversion coefficients (DCCs) for 15 reference organisms, animals and plants, either terrestrial, amphibian, or aquatic, and six radionuclides ((14)C, (90)Sr, (60)Co, (137)Cs, (238)U, and (241)Am). The results were compared with the reference values reported in Publication 108 of the International Commission on Radiological Protection, in which a different calculation approach for DCCs was employed. The results demonstrate that the present analytical method, originally intended for applications in internal dosimetry of nuclear medicine therapy, gives consistent results for all the beta-, beta-gamma-, and alpha-emitting radionuclides tested in a wide range of organism masses, between 8 mg and 1.3 kg. The applicability of the method proposed can take advantage from its ease of implementation in an ordinary electronic spreadsheet, allowing to calculate, for virtually all possible radionuclide emission spectra, the DCCs for ellipsoidal models of non-human living organisms in the environment.

222Rn, 220Rn and other dissolved gases in mineral waters of southeast Brazil

This paper describes the natural radioactivity due to 222Rn and 220Rn in mineral waters occurring at São Paulo and Minas Gerais states, Brazil, that are extensively used for drinking in public places, bottling and bathing purposes, among other. The measurements of these alpha-emitting radionuclides were also accompanied by the monitoring of temperature and some dissolved gases (O2, CO2 and H2S) in 75 water sources located in 14 municipalities of those states. Eight water sources yielded 220Rn activity concentration values below the detection limit of 4 mBq/L. On other hand, 222Rn activity concentration values exceeding the WHO guidance level of 100 Bq/L in drinking-water for public water supplies were found in two springs, named Villela and Dona Beja, whose discharge occurs in areas characterized by the presence of enhanced levels of natural radioelements in rocks. The obtained results were compared with the guidelines of the Brazilian Code of Mineral Waters (BCMW) that was established in 1945 and is still in force in the country. The 222Rn and 220Rn activity concentration data allowed perform dose radiation calculations based on the potential alpha energy concentration (PAEC), whose implications for health risk have been also considered in this paper.

Screening Foods for Radionuclide Contamination Via Analysis of Composited Analytical Portions

A procedure is presented for screening foods for radionuclide contamination. It was developed by the U.S. Food and Drug Administration (U.S. FDA) to be an option for augmenting analytical capability following a major radiological contamination event involving beta- or alpha-emitting radionuclides. The expected application of this procedure would be during late-phase monitoring, after initial monitoring suggests an area is contamination-free or levels are negligible but additional confirming data are desired. When food is taken from multiple samples and a composite analytical portion is prepared and analyzed using a quantitative method, it is possible to show that radionuclide activity levels are below a regulatory limit for a number of samples simultaneously. Although radionuclide activity levels are not obtained for individual samples, the number of samples that can be processed can be increased dramatically. In application, a limited number of selected samples would be analyzed using the usual unmodified quantitative method while the screening method would be used to provide supporting information for bulk quantities of samples. The procedure involves combining equal-mass portions from a number (n) of food samples to make a composite analytical portion, which is then analyzed using a quantitative method. Instead of comparing results with the regulatory limit, they are compared with a screening level equal to 1/n of the regulatory limit. If the observed activity concentration for the composite analytical portion is below the screening level, then the radionuclide levels are below the regulatory limit for all samples represented by it. Screening throughput will therefore depend on n. For n = 2, 3, etc., sample throughput will double, triple, etc., respectively. The maximum number of samples that may be combined is subject to limitations such as those associated with sample nonhomogeneity, detection capability, and the need to be able to discern abnormal radioactivity from that typical for a potentially-affected area.

Retracted Article: Selective Uptake of Uranium,Plutonium and Americium on Hydrogen Titanate Nanotubes

Hydrogen titanate nanotubes (HTNT) were prepared by hydrothermal method and characterized by SEM, TEM, XRD. The sorption efficiencies for alpha-emitting radionuclides 239Pu, 233U and 241Am were investigated. All three radionuclides studied were completely taken up by the synthesized HTNT between pH 1.00 to 6.00 from their mCi/L or mg/L feed concentration. The sorption process was sufficiently fast (complete uptake within an hour) and the standard free energy change accompanying the reaction was having very large negative value indicating it to be both thermodynamically and kinetically favourable. The sorption isotherms indicated predominant uptake of the radioactive metal ions in the solid phase of the exchanger at lower feed concentrations and linear Kielland plots with positive slopes indicated favourable exchange of the metal ions by the H+ ions in HTNT with the progress of the reaction. The Kielland plots suggested selective sorption of 233U , 239Pu and 241Am when their equivalent fractions in the solid was greater than 0.02, 0.015 and 5.0 ×10-4 , respectively and it was confirmed for americium uptake with interference studies. Even 5.00 g/L concentration of hydrogen titanate yielded 86 % sorption of 241Am after 15 minute and quantitative sorption after one hour of equilibration. The high Kd values suggest that the nano-titanate is potentially capable of removing americium, plutonium and uranium from large volumes of aqueous solutions.

Radiochemical characterization of mineral waters for a European interlaboratory comparison

The objective of this work was to select waters as realistic test items for an interlaboratory comparison on gross alpha/beta measurement in drinking waters. For this reason, a preliminary radioanalytical survey studying the naturally occurring alpha emitting radionuclides was carried out in 11 popular and regularly consumed mineral waters from the European market. The activity concentrations of the main naturally occurring alpha-emitting radionuclides (226Ra, 210Po, 234U, 235U, 238U and 228Th) were determined by using alpha spectrometry after separation from the matrix elements. Additionally, the committed effective dose was also estimated from the water consumption. Average activity concentrations of radionuclides in the mineral waters were in the following order: 226Ra>234U>238U>210Po>228Th>235U. The estimated committed effective doses for the analyzed mineral water samples are in the range 2.5–134.2μSv a−1 with an average 41.5μSv a−1, which is well below 100μSv a−1, the total indicative dose recommended by EC/WHO for drinking water (excluding mineral waters). Only one mineral water sample did not meet this requirement, its constant consumption would result in a dose higher than 100μSv a−1, mainly due to the contribution of 226Ra and 210Po. Apart from the main radiological characteristics of the analyzed waters, this study provides additional information for consumers and authorities about the potential internal exposure risk from mineral water intake. Based on the radionuclide composition and the total dissolved solids of the mineral waters two candidates were selected as potential test items for an interlaboratory comparison exercise.

Absorbed fractions for alpha particles in ellipsoidal volumes

Internal dosimetry of alpha particles is gaining attention due to the increasing applications in cancer treatment and also for the assessment of environmental contamination from radionuclides. We developed a Monte Carlo simulation in GEANT4 in order to calculate the absorbed fractions for monoenergetic alpha particles in the energy interval between 0.1 and 10 MeV, uniformly distributed in ellipsoids made of soft tissue. For each volume, we simulated a spherical shape, three oblate and three prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a ‘generalized radius’ was found; and the dependence of the fit parameters on the alpha energy is discussed and fitted by parametric functions. With the proposed formulation, the absorbed fraction for alpha particles in the energy range explored can be calculated for volumes and for ellipsoidal shapes of practical interest. This method can be applied to the evaluation of absorbed fraction from alpha-emitting radionuclides. The contribution to the deposited energy coming from electron and photon emissions can be accounted for exploiting the specific formulations previously introduced. As an example of application, the dosimetry of 213Bi and its decay chain in ellipsoids is reported.

Fluorescence-Assisted Gamma Spectrometry for Surface Contamination Analysis

A fluorescence-based alpha-gamma coincidence spectrometry approach has been developed for the analysis of alpha-emitting radionuclides. The thermalization of alpha particles in air produces UV light, which in turn can be detected over long distances. The simultaneous detection of UV and gamma photons allows detailed gamma analyses of a single spot of interest even in highly active surroundings. Alpha particles can also be detected indirectly from samples inside sealed plastic bags, which minimizes the risk of cross-contamination. The position-sensitive alpha-UV-gamma coincidence technique reveals the presence of alpha emitters and identifies the nuclides ten times faster than conventional gamma spectrometry.

Operational Experience of Continuous Air Monitoring of Smoke for 239Pu during a Wildfire

Smoke from a wildfire in northern New Mexico that moved along the border of the Los Alamos National Laboratory (LANL) was monitored for ²³⁹Pu in the event that the fire might cross into LANL property containing locations with low, but greater than background, levels of ²³⁹Pu and other alpha-emitting radionuclides. Three Environmental Continuous Air Monitors (ECAMs) in operation at LANL at the time of the fire provided near real-time measurements of the ²³⁹Pu in the smoke. Sampling data from routine measurements of PM-10 and PM-2.5 concentrations in the city of Los Alamos showed that smoke in the air rose during the fire to several hundred μg m⁻³, which produced limited visibility (several hundred meters) and resulted in poor air quality alerts for about a week-long period. Previous studies have shown that airborne dust can significantly impair continuous air monitors, so the purpose of this study was to assess the performance of the ECAMs under smoky conditions, which is important for many emergency response scenarios. Additionally, ECAMs are not required to be tested in smoke by ANSI standards, so there is little to no published data on performance of any ECAM while sampling smoke. Results show that the deployed ECAMs had reduced flow as the filter clogged with fine particles, but the goodness-of-fit parameter of the peak shape fitting algorithms and the minimum detectable concentration and dose were not impacted until the flow was reduced by more than about 20%, and even then they were within tolerable limits. Overall, ECAM performance was not impacted during the fire even under heavy smoke conditions and fluctuating radon levels, though changing the filters to limit any reductions in flow to less than 20% would maintain optimal ECAM performance.

Experimental therapeutics in prostate cancer: where are we now and where do we need to go

Experimental therapeutics in prostate cancer: where are we now and where do we need to go

Portable alpha spectrometer

Many portable devices have been designed to detect γ-rays or alpha and beta particles. Most of the α-particle detectors give the total count as a result, without identifying the radionuclides existing in the sample. The development of a device allowing rapid and straightforward α-particle spectrometry would be very useful for detecting the radioactive contents of unknown samples. This work describes the construction of a portable device using silicon semiconductor detectors designed to rapidly detect and possibly identify alpha-emitting radionuclides.

Development of decay energy spectroscopy using low temperature detectors

We have developed a high-resolution detection technique for measuring the energy and activity of alpha decay events using low-temperature detectors. A small amount of source material containing alpha-emitting radionuclides was enclosed in a 4π metal absorber. The energy of the alpha particles as well as that of the recoiled nuclides, low-energy electrons, and low-energy x-rays and γ-rays was converted into thermal energy of the gold absorber. A metallic magnetic calorimeter serving as a fast and sensitive thermometer was thermally attached to the metal absorber. In the present report, experimental demonstrations of Q spectroscopy were made with a new meander-type magnetic calorimeter. The thermal connection between the temperature sensor and the absorber was established with annealed gold wires. Each alpha decay event in the absorber resulted in a temperature increase of the absorber and the temperature sensor. Using the spectrum measured for a drop of 226Ra solution in a 4π gold absorber, all of the alpha emitters in the sample were identified with a demonstration of good detector linearity. The resolution of the 226Ra spectrum showed a 3.3keV FWHM at its Q value together with an expected gamma escape peak at the energy shifted by its γ-ray energy.

The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides

Targeted α-emitting drugs are promising for cancer therapy, but cannot be effectively imaged by conventional techniques. Cerenkov luminescence imaging (CLI) has previously been shown capable of imaging β+- and β−-emitting radionuclides in vivo and could have the potential to image α-emitters. Cerenkov light production from α-emitters is through Compton scattering and from farther down the decay chain. This causes the Cerenkov production to vary in time and depend on sample geometry, complicating the interpretation of CLI images. We used the simulation toolkit Geant4 to predict the Cerenkov light output from five α-emitting radionuclides that have therapeutic potential: 225Ac, 230U, 213Bi, 212Bi and 212At. We found that 225Ac, 213Bi and 212Bi produced an order of magnitude more Cerenkov light than 18F. However, the light from 225Ac is delayed from the initial decay, possibly decreasing the correlation of the drug and light source. This indicates that CLI will not be helpful in the development of some α-emitting drugs.

Sodium iodide symporter for nuclear molecular imaging and gene therapy: from bedside to bench and back.

Molecular imaging, defined as the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms, can be obtained by various imaging technologies, including nuclear imaging methods. Imaging of normal thyroid tissue and differentiated thyroid cancer, and treatment of thyroid cancer with radioiodine rely on the expression of the sodium iodide symporter (NIS) in these cells. NIS is an intrinsic membrane protein with 13 transmembrane domains and it takes up iodide into the cytosol from the extracellular fluid. By transferring NIS function to various cells via gene transfer, the cells can be visualized with gamma or positron emitting radioisotopes such as Tc-99m, I-123, I-131, I-124 and F-18 tetrafluoroborate, which are accumulated by NIS. They can also be treated with beta- or alpha-emitting radionuclides, such as I-131, Re-186, Re-188 and At-211, which are also accumulated by NIS. This article demonstrates the diagnostic and therapeutic applications of NIS as a radionuclide-based reporter gene for trafficking cells and a therapeutic gene for treating cancers.

An accurate method to measure alpha-emitting natural radionuclides in atmospheric filters: Application in two NORM industries

In this work, an accurate method for the measurement of natural alpha-emitting radionuclides from aerosols collected in air filters is presented and discussed in detail. The knowledge of the levels of several natural alpha-emitting radionuclides (238U, 234U, 232Th, 230Th, 228Th, 226Ra and 210Po) in atmospheric aerosols is essential not only for a better understanding of the several atmospheric processes and changes, but also for a proper evaluation of the potential doses, which can inadvertently be received by the population via inhalation. The proposed method takes into account the presence of intrinsic amounts of these radionuclides in the matrices of the quartz filters used, as well as the possible variation in the humidity of the filters throughout the collection process. In both cases, the corrections necessary in order to redress these levels have been evaluated and parameterized. Furthermore, a detailed study has been performed into the optimisation of the volume of air to be sampled in order to increase the accuracy in the determination of the radionuclides. The method as a whole has been applied for the determination of the activity concentrations of U- and Th-isotopes in aerosols collected at two NORM (Naturally Occurring Radioactive Material) industries located in the southwest of Spain. Based on the levels found, a conservative estimation has been performed to yield the additional committed effective doses to which the workers are potentially susceptible due to inhalation of anthropogenic material present in the environment of these two NORM industries.