Alpha Radionuclides Research Articles

Intercomparison exercise on difficult to measure alpha radionuclides in spent ion exchange resin

In radiochemical analysis of decommissioning waste, reference materials are not commercially available and consequently intercomparison exercises are needed for method validations. This paper reports the results from an intercomparison exercise focusing on analyses of α-emitter radionuclides in spent ion exchange resin. The exercise and statistical analysis of the submitted results were carried out based on ISO 13528 standard according to which the assigned values were calculated from the participant’s results and the performances were assessed using z-scores, which showed excellent performance for all 241Am analyses, good performance for 238Pu analyses, tolerable performance for 239,240Pu analyses, and questionable 243,244Cm analyses.

Phase I dose-escalation results of prostate-specific membrane antigen-targeted radionuclide therapy (PSMA-TRT) with alpha-radiolabeled antibody 225Ac-J591 and beta-radioligand 177Lu-PSMA I&T.

5018 Background: PSMA may be targeted by antibodies (mAb) or small molecules (SML), with different kinetics and biodistribution. mAb with longer circulation time and marrow exposure, but decreased access to luminal PSMA expression (e.g. salivary glands, intestine, kidney). SML diffuse to all sites of PSMA expression and then excreted. Alpha radionuclides emit more energy over shorter range vs beta. Pre-clinical data combining mAb and SML supports synergy, with enhanced uptake and retention of SML. Here, we present phase I dose-escalation results of a phase I/II trial investigating combo 225Ac-J591 with 177Lu-PSMA-I&T (aka PNT2002). Methods: Eligibility criteria include progressive mCRPC, ≥1 prior AR pathway inhibitor (ARPI), prior chemo (or unfit/refuse), ≥1 lesion with SUVmax >liver. Doses: 177Lu-PSMA-I&T (6.8 GBq); 225Ac-J591 (30, 35, or 40 KBq/kg), up to 2 doses of combo TRT 8 weeks (wks) apart with 177Lu SPECT following each dose. Primary objectives: dose-limiting toxicity (DLT) and recommended phase II dose; phase II will test the proportion of patients (pts) obtaining >50% PSA decline (PSA50). DLT defined as G4 myelosuppression lasting >1 wk, Gr>2 non-hematologic adverse event (AE), any Gr attributed AE delaying therapy >3 wks. Additional endpoints include progression-free and overall survival, radiographic response rate, safety, circulating tumor cell (CTC) changes, pt reported outcomes, PSMA imaging, blood/tissue correlatives. Results: 18 pts treated (6 at each dose level); 3 did not receive the 2nd dose due to progressive disease or withdrawal. Median age 70 (range 54-86), PSA 54.4 (2.43-9614). 13 (72%) with bone, 9 (50%) lymph node, 2 (11%) liver, 2 (11%) lung mets. 10 (56%) pts CALGB risk category high, 7 (39%) intermediate, 1 low. Previous therapies: 11 (61%) with >1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223. 2 of 6 pts with DLT at 40 KBq/Kg (Gr 2 or 3 thrombocytopenia delaying cycle 2 by >3 wk); no DLT observed in other cohorts. As submission, 7 pts (39%) remain on study, including 1 without progression at 16 months and another with undetectable PSA at 10 months. With follow up ongoing, 17 (94%) with PSA decline, 9 (50%) with PSA50. Of those with paired CTC counts, 4 of 5 (80%) converted from unfavorable to favorable CTC count, 4 of 8 (50%) from detectable to undetectable, 1 of 2 (50%) remained undetectable. AEs include 3 (17%) neutropenia (all Gr <2), 12 (67%) thrombocytopenia (3 Gr 3), 10 (56%) anemia (3 Gr 3), 10 (56%) pain flare (1 Gr3 in pt with cord compression), 12 (67%) xerostomia (one Gr2), 11 (61%) nausea (all Gr 1), 9 (50%) fatigue (all Gr 1). Conclusions: The combination of dual-PSMA targeting with mAb + SML and alpha + beta is feasible with follow up ongoing. Efficacy will formally be tested in the upcoming phase II portion of the study with 225Ac-J591 at 35 KBq/Kg and 177Lu-PSMA I&T at 6.8 GBq. Clinical trial information: NCT04886986 .

Development of an ultrahigh resolution real time alpha particle imaging system for observing the trajectories of alpha particles in a scintillator

High-resolution imaging of alpha particles is required in the detection of alpha radionuclides in cells or small organs for the development of radio-compounds for targeted alpha-particle therapy or other purposes. We developed an ultrahigh resolution, real time alpha-particle imaging system for observing the trajectories of alpha particles in a scintillator. The developed system is based on a magnifying unit and a cooled electron multiplying charge-coupled device (EM-CCD) camera, combined with a 100-µm-thick Ce-doped Gd3Al2Ga3O12 (GAGG) scintillator plate. Alpha particles from an Am-241 source were irradiated to the GAGG scintillator and imaged with the system. Using our system, we measured the trajectories of the alpha particles having different shapes in real time. In some of these measured trajectories, the line shapes of the alpha particles that flew in the GAGG scintillator were clearly observed. The lateral profiles of the alpha-particle trajectories were imaged with widths of ~ 2 µm. We conclude that the developed imaging system is promising for research on targeted alpha-particle therapy or other alpha particle detections that require high spatial resolution.

Nano-hydroxyapatite radiolabeled with radium dichloride [223Ra] RaCl2 for bone cancer targeted alpha therapy: In vitro assay and radiation effect on the nanostructure

The use of targeted alpha therapy (TAT) for bone cancer is increasing each year. Among the alpha radionuclides, radium [223Ra]Ra+2 is the first one approved for bone cancer metastasis therapy. The development of novel radiopharmaceutical based on [223Ra]Ra+2 is essential to continuously increase the arsenal of new TAT drugs. In this study we have developed, characterized, and in vitro evaluated [223Ra] Ra-nano-hydroxyapatite. The results showed that [223Ra] Ra-nano-hydroxyapatite has a dose-response relationship for osteosarcoma cells and a safety profile for human fibroblast cells, corroborating the application as a radiopharmaceutical.

Targeted thorium-227 conjugates as treatment options in oncology.

Targeted alpha therapy (TAT) is a promising approach for addressing unmet needs in oncology. Inherent properties make α-emitting radionuclides well suited to cancer therapy, including high linear energy transfer (LET), penetration range of 2-10 cell layers, induction of complex double-stranded DNA breaks, and immune-stimulatory effects. Several alpha radionuclides, including radium-223 (223Ra), actinium-225 (225Ac), and thorium-227 (227Th), have been investigated. Conjugation of tumor targeting modalities, such as antibodies and small molecules, with a chelator moiety and subsequent radiolabeling with α-emitters enables specific delivery of cytotoxic payloads to different tumor types. 223Ra dichloride, approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with bone-metastatic disease and no visceral metastasis, is the only approved and commercialized alpha therapy. However, 223Ra dichloride cannot currently be complexed to targeting moieties. In contrast to 223Ra, 227Th may be readily chelated, which allows radiolabeling of tumor targeting moieties to produce targeted thorium conjugates (TTCs), facilitating delivery to a broad range of tumors. TTCs have shown promise in pre-clinical studies across a range of tumor-cell expressing antigens. A clinical study in hematological malignancy targeting CD22 has demonstrated early signs of activity. Furthermore, pre-clinical studies show additive or synergistic effects when TTCs are combined with established anti-cancer therapies, for example androgen receptor inhibitors (ARI), DNA damage response inhibitors such as poly (ADP)-ribose polymerase inhibitors or ataxia telangiectasia and Rad3-related kinase inhibitors, as well as immune checkpoint inhibitors.

Advances in Targeted Alpha Therapy: Preparation and Separation of Alpha Radionuclides

Advances in Targeted Alpha Therapy: Preparation and Separation of Alpha Radionuclides

Review of the Gross Alpha for Characterization of Radioactive Waste

In this study, we discussed the limitations of gross alpha measurements for the characterization of radioactive wastes produced in nuclear facilities through experimental tests and Monte Carlo N-particle transport simulations. The determination of gross alpha is essential for the disposal of radioactive waste produced in nuclear facilities in Korea. The measurements of gross alpha are easy to perform and yield rapid analytical results, but it cannot be used for quantitative analysis. The error of counting efficiency for gross alpha with various masses of the deposit on planchets using KCl and 241Am was determined. The relative deviation of the counting efficiency in samples having the same mass was 20%. Uranium was extracted from the soil through acid leaching and extraction chromatography, and the concentration of U determined by inductively coupled plasma–mass spectrometry (ICP-MS) was compared with the results for gross alpha. The gross alpha was underestimated by 50% compared to the U concentration by ICP-MS. The counting efficiency depended on the energy from the alpha emitters, which differed by up to three times in determination of the counting efficiency depending on the kinds of alpha radionuclides of interest. Therefore, the gross alpha is not compatible with the sum of radioactivity for each alpha emitter and is suitable as a screening method.

Synthesis and luminescent properties of bismuth borosilicate glass doped with Eu3+

The work was aimed at development of glasses for encapsulation of self-glowing crystals, doped with alpha radionuclides. Bismuth borosilicate-based glass systems doped with Eu3+, В2О3-ЅіO2-Аl2О3-Bi2O3-MO (where M = Ba, Sr and Zn) (Si–Bi -x), with various concentrations of activator were studied. The optimal synthesis conditions were selected, the composition of the obtained glasses was investigated using electron-probe microanalysis technique. Optical properties of glasses were investigated using the following methods – cathodoluminescence, photoluminescence and absorption. The range of the optimal activator concentration was determined.

Feasibility evaluation of a direct detection method of alpha particles in water using YGAG plate with pulse shape analysis

Ce doped (YGd)3(GaAl)5O12:Ce (YGAG) is a ceramic scintillator with high light output, and its decay times are different between alpha particles and gamma photons or beta particles. This characteristic may be applied to the direct measurement of alpha particles in water where the gamma photons or beta particles become background counts. Thus we proposed a radiation detector using a YGAG plate dipped in water that contained alpha radionuclides to detect alpha particles in water. The scintillation photons from the YGAG plate were detected by a position sensitive photomultiplier tube (PSPMT) set in water that contained alpha radionuclides. A YGAG plate (20 × 20 × 0.5 mm) was set on the bottom of a glass cup filled with water containing alpha radionuclides that emit alpha particles. The alpha particles near the YGAG plate were detected by the scintillator, and the scintillation light was detected by the PSPMT . For radon-containing water sampled from a hot spring, pulse shape spectra showed two peaks: one for the alpha particles and another for the beta particles and the gamma photons. By pulse shape discrimination for the peak of the alpha particles, their count rate decreased with a decay of Rn-222 (3.8 days). For tap water, the pulse shape distribution showed only one peak and the count rate was almost constant, indicating these counts were mainly from the background beta particles or gamma photons. We could show a detection principle for alpha radionuclides in water and this detection principle for alpha radionuclides in water might be a new method for estimating the alpha radionuclide concentration in water.

Detection of alpha radionuclides in air from patients during Ra-223 alpha radionuclide therapy

Ra-223 has recently been introduced to alpha radionuclide therapy. According to the decay scheme of Ra-223, an inert gas, Rn-219 is released from patients during alpha radionuclide therapy and its daughter radionuclides may accumulate around the patient. However, the concentration of these radon daughters during alpha radionuclide therapy was not obvious. Here, we first detected the radon daughters of Rn-219 around patients during alpha radionuclide therapy. While the Ra-223-administered patients were in a room for ~1.5 hours, the radon daughter concentration increased to 4 to 5 times higher than without the patients. When the patients were in the room, the energy spectra of the alpha particles in the air showed the peak of the radon daughter of Rn-219, Bi-211 (6.6 MeV), which was different from that without the patients. We conclude that the daughter radionuclides of Rn-219 are accumulated around the patient, and the concentration was higher than that of the natural radon daughters. However, the increase in levels of alpha emitters, while detectable, is lower than the daily variations and thus is likely not a source of concern for radiation exposure.

Alpha spectrometry in radiochemical analysis and its application in the study of the natural environment

<p>Alpha spectrometry is a highly sensitive and modern measurement technique which can be used to radiochemical and radiological studies of the natural environment. In the paper were presented the results on application of alpha spectrometry in the study for determination of natural (<sup>210</sup>Po, <sup>210</sup>Pb, <sup>234</sup>U, <sup>238</sup>U) and artificial (<sup>238</sup>Pu, <sup>239+240</sup>Pu and <sup>241</sup>Pu) alpha and beta radionuclides in environment of Poland and Baltic Sea. Amongst the radionuclides, alpha particle emitters play the most important role as they are highly radiotoxic to organisms. The concentrations of alpha radionuclides in the environmental samples of Poland are characterized based on the environmental materials collected between 1998 and 2009. Biogeochemistry of polonium, uranium and plutonium in the southern Baltic Sea ecosystem combined with the use of radioactive disequilibrium <sup>210</sup>Po/<sup>210</sup>Pb, <sup>234</sup>U/<sup>238</sup>U and <sup>238</sup>Pu/<sup>239+240</sup>Pu and <sup>241</sup>Pu/<sup>239+240</sup>Pu allows you to identify the sources of these radionuclides in natural ecosystems. It also allows to determine their circulation in the environment (e. g. to assess the impact of the Chernobyl nuclear accident on the radioactive contamination of Poland).</p><p class="APodstawowy"> </p>

Dynamics of body burdens and doses due to internal irradiation from intakes of long-lived radionuclides by residents of Ozyorsk situated near Mayak PA

This paper presents and discusses new autopsy results and other historic data from earlier autopsies and environmental monitoring linked to releases from the Mayak PA facilities in the Chelyabinsk oblast in the southern Urals. The focus is on residents of the town of Ozyorsk located near to Mayak PA and the dynamics of body burdens and radiation doses from inhalation of plutonium alpha and americium-241, and ingestion of strontium-90 and caesium-137. It is demonstrated that accumulation and exposure from these radionuclides was mainly due to unplanned releases in the 1950s and 60s. The mean content of plutonium alpha at the time of autopsy of people commencing residence in Ozyorsk from 1949 to 1959 was about 3.5 Bq, falling to 0.2 Bq in those arriving after 1990. A reducing trend was also seen for 241Am. The highest 90Sr content in Ozyorsk residents was measured in 1967. The 137Cs body content of residents arriving in Ozyorsk at any time was in almost all cases below the limit of detection. The committed effective dose from internal exposure to these long-lived radionuclides which would have been accumulated in Ozyorsk residents if present from 1949 to 2013 is estimated to be 13 mSv. This dose is primarily attributed to intakes during 1949 to 1959 when the annual effective dose rate was approximately 1 mSv y−1. The current value is about 0.1 mSv y−1. This dose is about 20 times higher than the dose from global man-made fallout, which is about 0.005 mSv y−1 at present, but much lower than that from natural background radiation, i.e. about 2 mSv y−1.The experience gained from this work and continuing activities can contribute to the development of improved international guidance in legacy situations, particularly as regards the provision and use of monitoring data to test and thereby build confidence in prognostic models for radiation conditions and potential future exposures. The scope includes evidence for the rate of reduction in radionuclide concentrations in environmental media and in their bioavailability, resuspension of long-lived alpha radionuclides, uptake of 90Sr and 137Cs in the food-chain, and confirmation of cumulative uptake via autopsy and whole body counting measurements. Continuing investigations will thus support decisions on future planned releases and contribute to planning of remediation of other areas affected by historic releases.

Characterization of the extraction properties of the selected extraction sorbents TRU, TEVA, UTEVA and DIPHONIX

The paper describes the extraction characteristics of selected alpha radionuclides by means of extraction chromatography of the selected resins—TRU, TEVA, UTEVA, DN and DIPHONIX. The aim was to investigate the choice of mobile-phase and especially the effect on the percentage of extraction, the conditions leading to degradation of extraction sorbents and also to determine the synergistic effect of different cations added to mobile-phase.

Using α radiation to boost cancer immunity?

Radioimmunotherapy aims to deliver radiation directly to cancer cells by means of a tumor specific vector coupled to a radionuclide. Alpha radionuclides are very potent agents to treat disseminated cancer and metastasis. We have demonstrated that α radiation can also induce immunogenic cell death, reinforcing interest in their clinical development.

Mycoremediation: the study of transfer factor for plutonium and americium uptake from the ground

In our scientific research we have monitored mycoremediation’s properties of oyster mushrooms in cultivation on the soil what is contaminated by solutions with radioactive isotopes of 239Pu and 241Am with known activity. We monitored specific activities of absorbed radionuclides in fruiting bodies and chemical forms of radionuclides which were compared to calculated specific activities of two background samples of oyster mushrooms intended for consumer purpose. We determined distributive coefficients between the ground and the fruiting body of oyster mushrooms. The average value which was obtained for the transfer factor for plutonium was 0.72 and for americium 3.97. To evaluate a quantity of absorbed radionuclides we used a method of liquid extraction. The emitting alpha radiation of alpha radionuclides was detected by spectrometry. For defining individual fractions of plutonium and americium that are contained in mushroom bodies was used the sequential leaching method.

Reassessment of individual dosimetry of long-lived alpha radionuclides of uranium miners through experimental determination of urinary excretion of uranium

Urinary excretion of uranium of 40 uranium miners was determined by the high-resolution inductively coupled mass spectrometry method. The concentration of uranium in the urine of the miners was converted to daily excretion of (238)U either under the assumption that the daily urinary excretion is 1.6 l or daily urinary excretion of creatinine is 1.7 g and compared with the excretion of (238)U calculated with a biokinetic model. Input data to the excretion model were derived from personal three- component ALGADE dosemeters, using the component for the estimation of inhalation of long-lived alpha radionuclides. Experimentally found contents of uranium in the urine of uranium miners are generally lower than the modelled ones, which means that the dosimetric approach is conservative. The uncertainty of inhalation intakes, derived from the measurements of filters from personal dosemeters, and the uncertainty of the concentration of uranium in the urine are discussed.

The radiochemical contamination (210Po and 238U) of zone around phosphogypsum waste heap in Wiślinka (northern Poland)

The aim of this work was the determination of the impact of phosphogypsum waste heap in Wiślinka (northern Poland) for radiological protection of zone around waste heap. These studies are very important for the estimation of natural alpha radionuclides contents in the vicinity of phosphogypsum waste heap and for environmental pollution assessment of this area. The process of bioaccumulation of radionuclides in interior plants parts prove to examine their origin sources, too. The activity of 210Po, 234U, and 238U were measured using an alpha spectrometer. The values of uranium and polonium concentration in water with immediate area of waste heap are considerably higher than in the waters of the Martwa Wisła river. The values of activity ratio 234U/238U are approximately about one in the phosphogypsum (0.97 ± 0.05) and in the water of retention reservoir and pumping station (0.92 ± 0.01 and 0.99 ± 0.08), while in the water from the Martwa Wisła river they are slightly higher than one (1.03 ± 0.07 and 1.17 ± 0.06). In the analyzed plants species the highest amounts of polonium and uranium were found in ruderal plants samples (between 51 ± 1 and 89 ± 1 for 210Po; between 36 ± 3 and 68 ± 3 for 238U) as well as hygrophilous plant samples (18 ± 1 and 84 ± 3; 42 ± 2 and 130 ± 4, respectively for 210Po and 238U). The more amounts of 210Po and 238U radionuclides were accumulated mainly in the roots of plant species in comparison to green parts. The general conclusion of realized study is higher influence of phosphogypsum on radioactive contamination of environmental zone around heap waste in Wiślinka (northern Poland).

Content of uranium in urine of uranium miners as a tool for estimation of intakes of long-lived alpha radionuclides

Uranium in the urine of 10 uranium miners (hewers), 27 members of general population and 11 family members of miners was determined by the High-Resolution ICP-MS method. Concentration of uranium in urine of the miners was converted to daily excretion of (238)U under the assumption that the daily excretion of urine is 2 l and compared with the modelled excretion of (238)U. Daily excretion of (238)U was modelled using input data from personal dosemeters from a component for measurement of intake of long-lived alpha radionuclides. A reasonable agreement between evaluated and measured values was found. The uncertainty of inhalation intakes, derived from measurements of filters from personal dosemeters, and uncertainty of concentration of uranium in urine are discussed.

Detoxification of AM-241 solutions by humic substances: bioluminescent monitoring

The study addresses the effect of humic substances on marine luminous bacteria Photobacterium phosphoreum exposed to Am-241 (3,000BqL(-1), water solution). Luminescent intensity of the bacteria was applied as a marker of their physiological activity. Humic substances have been found to reduce the effect of Am-241 on luminescence, decrease damage to cells, and change distribution of Am-241 between bacterial cells and intercellular media. It was shown that water-soluble humic substances, being products of natural transformation of organic substances in soil and bottom sediments, can serve as protecting agents for water microorganisms exposed to alpha radionuclides.

The inflow of uranium 234U and 238U from the Vistula River catchment area to the Baltic Sea

Abstract In the study, the activities of uranium 234U and 238U in the Vistula River water samples which were collected from November 2002 to October 2003, were measured using alpha spectrometry. In winter, the highest concentration of uranium isotopes and total uranium was in the Vistula River water from Malbork (13.13±0.22 Bq m−3 for 234U, 12.45±0.21 Bq m−3 for 238U and 1.02±0.30 mg m−3 for total uranium), and the lowest was in water from Dęblin (1.73±0.07 Bq m−3 for 234U, 1.55±0.07 Bq m−3 for 238U and 0.13±0.09 mg m−3 for total uranium). In analyzed river samples uranium isotopes 234U and 238U are not in the radioactive equilibrium state. The values of 234U/238U activity ratio lie between 1.05–1.70. During spring, the highest concentration of uranium isotopes and total uranium was found in the Vistula River water from Malbork (12.36±0.19 Bq m−3 for 234U, 10.77±0.17 Bq m−3 for 238U and 0.88±0.25 mg m−3 for total uranium), and the lowest was in water taken from Sandomierz (5.77±0.14 Bq m−3 for 234U) and Kraków (4.08±0.11 Bq m`−3 for 238U and 0.33±0.18 mg m−3 for total uranium). The values of 234U/238U activity ratio lie between 1.15–1.64. In summer, the highest concentration of uranium isotopes and total uranium was found in the Vistula River water samples taken from Malbork (8.22±0.21 Bq m−3 for 234U, 7.60±0.21 Bq m−3 for 238U and 0.62±0.29 mg m−3 for total uranium), and the lowest was in water from Sandomierz (6.37±0.12 Bq m−3 for 234U) and Kraków (3.56±0.19 Bq m−3 for 238U and 0.29±0.33 mg m−3 for total uranium). The values of 234U/238U activity ratio lie between 1.08–1.95. In autumn the highest concentration of uranium isotopes and total uranium was in the Vistula River water from Malbork (17.80±0.25 Bq m−3 for 234U, 15.12±0.23 Bq m−3 for 238U and 1.23±0.34 mg m−3 for total uranium) and the lowest was in water from Toruń (8.15±0.49 Bq m−3 for 234U) and Kraków (6.34±0.47 Bq m−3 for 238U and 0.52±0.78 mg m−3 for total uranium). The values of 234U/238U activity ratio lie between 1.10–1.74. Annually, the southern Baltic Sea is enriched by about 507 GBq uranium isotopes 234U and 238U, with 490 GBq going to the Gdańsk Bay and 16.5 GBq to Vistula Lagoon. The highest surface 238U runoff was observed in spring (to 1200 kBq km−2 quarter−1 for catchment´s area), the lowest in summer for Bug with Narew catchment´s area to 20 kBq km−2 quarter−1). These studies are very important for the inflow estimation of natural and anthropogenic alpha radionuclides to the Baltic Sea.