Search Results (72)

Background: In nuclear medicine, numerous cancer types are treated via internal irradiation with radiopharmaceuticals, including low-LET (linear energy transfer) beta-emitting radionuclides like Lu-177. In most cases, such treatments lead to low-dose exposure of organ systems with β-irradiation, which induces only few isolated DSBs (double-strand breaks) in the nuclei of hit cells, the most threatening DNA damage type. That damaging effect contrasts with the clustering of DNA damage and DSBs in nuclei traversed by high-LET particles (α particles, ions, etc.). Methods: After in-solution β-irradiation for 1 h with Lu-177 leading to an absorbed dose of about 100 mGy, we investigated the spatial nano-organization of chromatin at DSB damage sites, of repair proteins and of heterochromatin marks via single-molecule localization microscopy (SMLM) in PBMCs. For evaluation, mathematical approaches were used (Ripley distance frequency statistics, DBScan clustering, persistent homology and similarity measurements). Results: We analyzed, at the nanoscale, the distribution of the DNA damage response (DDR) proteins γH2AX, 53BP1, MRE11 and pATM in the chromatin regions surrounding a DSB. Furthermore, local changes in spatial H3K9me3 heterochromatin organization were analyzed relative to γH2AX distribution. SMLM measurements of the different fluorescent molecule tags revealed characteristic clustering of the DDR markers around one or two damage foci per PBMC cell nucleus. Ripley distance histograms suggested the concentration of MRE11 molecules inside γH2AX-clusters, while 53BP1 was present throughout the entire γH2AX clusters. Persistent homology comparisons for 53BP1, MRE11 and γH2AX by Jaccard index calculation revealed significant topological similarities for each of these markers. Since the heterochromatin organization of cell nuclei determines the identity of cell nuclei and correlates to genome activity, it also influences DNA repair. Therefore, the histone H3 tri methyl mark H3K9me3 was analyzed for its topology. In contrast to typical results obtained through photon irradiation, where γH2AX and H3K9me3 markers were well separated, the results obtained here also showed a close spatial proximity (“co-localization”) in many cases (minimum distance of markers = marker size), even with the strictest co-localization distance threshold (20 nm) for γH2AX and H3K9me3. The data support the results from the literature where only one DSB induced by low-dose low LET irradiation (<100 mGy) can remain without heterochromatin relaxation for subsequent repair. Full article

Background: α-emitting Peptide Receptor Radionuclide Therapy (α-PRRT) is emerging as a promising new generation of PRRT for neuroendocrine tumors (NETs), providing enhanced tumor cell cytotoxicity and reduced irradiation of adjacent healthy tissues due to its high linear energy transfer (LET) and short particle range. This review summarizes available clinical evidence on α-PRRT using different α-emitting isotopes, including actinium-225, lead-212, and bismuth-213, in somatostatin receptor (SSTR)-positive NETs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov, as well as major oncology congress abstracts (ENETS, ESMO, ASCO). Eligible studies included clinical trials evaluating α-PRRT in patients with advanced SSTR-positive NETs, reporting therapeutic response and adverse events. The primary endpoint was the objective response rate (ORR); secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Seven studies encompassing 150 patients were included. Treatment with [²²⁵Ac]Ac-DOTATATE yielded a pooled ORR of 50% and a DCR of 81.3% across 121 evaluable patients. The best responses were observed in patients who had previously responded to β-PRRT (ORR 70.4%, DCR 96.3%), while one-third of β-PRRT–refractory patients achieved partial or complete responses. [²¹²Pb]Pb-DOTAMTATE demonstrated an ORR of 56.8% and DCR of 100% in preliminary phase II results, though dysphagia was noted in 34% of patients. [²¹³Bi]Bi-DOTATOC and [²¹²Pb]Pb-VMT-α-NET studies also showed promising disease control with minimal grade ≥ 3 hematologic or renal toxicities. Across all studies, α-PRRT was well tolerated, with predominantly low-grade hematologic adverse events and no significant hepatic or renal toxicity. Conclusions: Clinical data to date indicate that α-PRRT offers meaningful therapeutic benefit in patients with metastatic or treatment-refractory NETs, achieving favorable response rates with manageable toxicity. Early results support α-PRRT as a potential first- or second-line therapeutic option. Ongoing phase III trials will be critical to confirm its long-term safety, survival outcomes, and role in routine clinical practice. Full article

The growing use of experimental radiopharmaceuticals for targeted radionuclide therapy (TRT) highlights the need for robust “in house” radiolabeling protocols. Among these, PSMA-ALB-56 is a PSMA ligand incorporating an albumin-binding moiety to enhance pharmacokinetics, which showed promise for prostate cancer treatment. This study investigated manual radiolabeling conditions of this vector molecule with lutetium-177 and developed a corresponding automated synthesis protocol. Manual experiments on low activities explored buffer systems and antioxidants, identifying sodium acetate buffer and L-methionine as optimal, achieving radiochemical purities above 97% with excellent stability over 48 h. However, when these conditions were transposed directly to an automated process on a GAIA^® module with activities > 2 GBq, radiochemical purity dropped below 70% due to significant radiolysis. This result emphasized that conditions optimized at low activities are not directly transferable to high-activity automated production, and highlighted the crucial role of antioxidant concentration. An optimized automated method was subsequently developed, integrating a solid-phase extraction purification step, higher antioxidant levels during radiolabeling and formulation, and a larger final product volume. These changes led to radiochemical purities above 98.9% and excellent product stability over 120 h for 3 test batches. The presence of high concentrations of methionine and ascorbic acid was essential to protect against radiolysis. This work underscores the importance of adjusting radiolabeling strategies during process scale-up and confirmed that antioxidant concentration is essential for successful ¹⁷⁷Lu radiolabeling. The optimized automated method developed here for [¹⁷⁷Lu]Lu-PSMA-ALB-56 may also be adapted to other radiopharmaceuticals in development for TRT. Full article

Phosphogypsum (PG) is a byproduct of the wet phosphoric acid (WPA) production process. Since PG originates from phosphate rock (PR), it holds various concentrations of heavy metal and radionuclide, posing an environmental threat because of its large production and long-term accumulation. In addition to toxic heavy metals, PG may also be an alternative source of rare earth elements (REEs), since over 60% of REEs in PR transfer to PG during acid digestion. With the increasing demand of phosphoric acid (PA), global PG generation is approaching 300 million tons annually. Since 1994, an estimated 6.73 billion tons of PG has been produced worldwide, with approximately 58% (approx. 3.7 billion tons) ending up in stacks. Assuming a conservative REE content of 0.1%, these stacks may hold over 3.7 million tons of REEs. This review discusses phosphoric acid production processes and the transfer of REEs from PR to PG. In addition, it also discusses the current REEs world reserves, their presence in primary and secondary sources, and their uses. The review critically evaluates the research that has been conducted so far and the recent innovations in REE recovery from PG, and discusses the challenges associated with scalability and raw material variability. Full article

Alpha therapy (TAT) relies on combining alpha-emitting radionuclides with specific cell-targeting vectors to deliver a high payload of cytotoxic radiation capable of destroying tumor tissues. TAT efficacy comes from the tissue selectivity of the targeting vector, the high linear energy transfer (LET) of the radionuclide, and the short range of alpha particles in tissues. Recent research studies have been directed to evaluate TAT on a preclinical and clinical scale, including evaluating damage to tumor tissues with minimal toxic radiation effects on surrounding healthy tissues. This review highlights the use of Actinium-225/Bismuth-213 radionuclides as promising candidates for TAT. Herein, we begin with a discussion on the production and supply of [²²⁵Ac]Ac/[²¹³Bi]Bi followed by the formulation of [²²⁵Ac]Ac/[²¹³Bi]Bi-radiopharmaceuticals using different radiolabeling techniques. Finally, we have summarized the preclinical and clinical evaluation of these potential radiotheranostic agents. Full article

Artisanal gold mining can enhance natural radioactivity in nearby environmental media. This study assessed health risks and environmental impacts associated with the release of natural radionuclides in Atiwa West, Ghana. Activities of naturally occurring radionuclides were measured in soil samples (Ra-226, Th-232, K-40) and water samples (Ra-226, Ra-228, K-40) by HPGe γ-spectrometry; Ra-226 in vegetation was estimated from soil activities using a transfer factor. The mean activity concentrations in soils were 22.1 ± 2.1 Bq/kg (Ra-226), 27.5 ± 2.3 Bq/kg (Th-232) and 198 ± 22 Bq/kg (K-40). At several water locations, Ra-226 and Ra-228 exceeded the WHO screening levels for drinking water of 1.0 Bq/L and 0.1 Bq/L, respectively. Radiological hazard indices attributable to inhalation and ingestion were evaluated. Overall, soil radiological risks were low; however, approximately 22% of sites recorded values above the global average annual gonadal dose equivalent (AGDE). In some locations, the committed effective dose from drinking water surpassed the WHO screening threshold of 0.1 mSv/y, with the associated excess lifetime cancer risk (ELCR) exceeding 2.9 × 10⁻⁴. Overall, the mining-affected waters presented a greater potential radiological impact than the soils, underscoring the need for water quality management and periodic monitoring in artisanal mining areas. Full article

Croatian agricultural legislation acknowledges the significance of radionuclides as pollutants in agricultural lands; however, it lacks specific thresholds or reference values for contamination levels, in contrast to other contaminants. This absence highlights the necessity for a comprehensive assessment of radionuclides across various agricultural systems in Croatia. This study investigates the transfer of radionuclides ¹³⁷Cs and ⁴⁰K from soil to agricultural crops throughout Croatia and estimates the consequent annual ingestion dose for the population. The samples collected comprised food crops and animal feed, with corresponding soil samples analyzed to calculate transfer factors. Activity concentrations of ¹³⁷Cs exhibited regional and crop-type variability, reflecting the uneven distribution of fallout and differing soil properties. Transfer factors were found to range from 0.003 to 0.06 for ¹³⁷Cs and from 0.15 to 3.1 for ⁴⁰K, with the highest uptake occurring in kidney beans. The total estimated annual effective ingestion dose was calculated to be a maximum of 0.748 mSv/year for children aged 2–7, predominantly attributable to ⁴⁰K. Given the homeostatic regulation of potassium in the human body, the dose associated with ¹³⁷Cs poses a more significant radiological concern. These findings underscore the need for radionuclide-specific agricultural legislation in Croatia and offer a baseline for recommending reference values and informing future regulations regarding agricultural soil contamination. Full article

Wild-growing edible mushrooms are known to bioaccumulate radionuclides from their environment, particularly the natural isotope potassium-40 (⁴⁰K) and anthropogenic cesium-137 (¹³⁷Cs). However, region-specific data for commercially relevant species in north-eastern Poland remain limited, despite the cultural and economic importance of mushroom foraging and export. This study aimed to assess the radiological safety of wild mushrooms intended for human consumption, with particular attention to regulatory compliance and potential exposure levels. In this study, 230 mushroom samples representing 19 wild edible species were analyzed using gamma spectrometry, alongside composite soil samples collected from corresponding foraging sites. The activity concentration of ¹³⁷Cs in mushrooms ranged from 0.94 to 159.0 Bq/kg fresh mass (f.m.), and that of ⁴⁰K from 64.4 to 150.2 Bq/kg f.m. None of the samples exceeded the regulatory limit of 1250 Bq/kg f.m. for ¹³⁷Cs. The highest estimated annual effective dose was 2.32 µSv from ¹³⁷Cs and 0.93 µSv from ⁴⁰K, with no exceedance of regulatory limits observed in any sample. A strong positive correlation was observed between ¹³⁷Cs activity in soil and mushroom dry mass (Spearman’s Rho = 0.81, p = 0.042), supporting predictable transfer patterns. Additionally, the implications of mushroom drying were assessed considering Council Regulation (Euratom) 2016/52, which mandates radionuclide levels in dried products be evaluated based on their reconstituted form. After such adjustment, even the most contaminated dried samples were found to comply with food safety limits. These findings confirm the radiological safety of wild mushrooms from north-eastern Poland and contribute novel data for a region with limited prior monitoring, in the context of current food safety regulations. Full article

Multidrug resistance (MDR) represents a major obstacle to successful chemotherapy and, due to overlapping defense mechanisms, such as enhanced DNA repair and the evasion of apoptosis, can also be associated with radioresistance. In this study, we investigated whether MDR breast cancer cells (MCF-7/CMF) exhibit reduced susceptibility to radiation-induced DNA fragmentation compared to their non-resistant parental counterpart (MCF-7). Using a nucleosome-based ELISA, we quantified the chromatin fragmentation in MCF-7 and MCF-7/CMF cells following their exposure to four radiopharmaceuticals: [^99mTc]pertechnetate, [¹³¹I]NaI (sodium iodide), [¹²⁵I]NaI, and the DNA-incorporating compound [¹²⁵I]iododeoxyuridine ([¹²⁵I]IdU). Each radioactive preparation was assessed across a range of activity concentrations, using a two-way ANOVA. For [^99mTc]pertechnetate and [¹³¹I]NaI, significantly higher DNA fragmentation was observed in the sensitive cell line, whereas [¹²⁵I]NaI showed no significant difference between the two phenotypes. In contrast to the other radiopharmaceuticals, [¹²⁵I]IdU induced greater fragmentation in resistant cells. This finding was supported by the statistical analysis (a 63.7% increase) and visualized in the corresponding dose–response plots. These results highlight the critical role of the intranuclear enrichment of Auger emitters and support further development of radiopharmaceuticals in accordance with this principle. Our data suggest that radiotoxicity is governed not by linear energy transfer (LET) alone, but, fundamentally, by the spatial proximity of the radionuclide to the DNA. Targeting tumor cell DNA with precision radiotherapeutics may, therefore, offer a rational strategy to overcome MDR in breast cancer. Full article

Tritium is a radioisotope that is extremely mobile in the biosphere and that can be transferred to the environment and to humans mainly via tritium oxide or tritiated water. Moreover, as is widely known, it is extremely difficult to detect in the environment. In the last decade, many studies and research activities have been performed to fill the knowledge gap on this radionuclide, the amount of which is expected to be increasingly released into the environment from nuclear installations in the near future. Considering this and the fact that the biological and environmental effects produced by tritium have been examined mainly from a medical and detection monitoring point of view, it is considered important to propose in this study a review of the critical aspects of tritium from the environmental, engineering, and waste management points of view. Identifying sources and effects of tritium, tritium materials and wastes containing tritium in the environment is also fundamental for planning the specific and necessary actions required for an effective waste management approach under, e.g., disposal conditions. The critical analysis of the published recent studies has allowed to evaluate, for example, that the expected rate of tritium generation in a fusion reactor is four orders of magnitude higher than that of LWRs, and the environmental release from a fusion reactor is 1.4–2.2‱, which is twice as much as from a heavy water reactor and more than two orders of magnitude higher than from a LWRs. Furthermore, with reference to the waste management strategy, it is emphasized, e.g., that the condensation of moisture inside vaults and the interaction of H₂O with the disposal body determine the formation of tritiated water, which is filtered through the concrete and eventually released into the environment. Consequently, in the selection of engineered barrier materials for repositories/disposal facilities, the use of a mixture of a framework and layered silicates is proposed to improve its absorption and filtering properties. Full article

Gamma-ray analysis is a widely used technique for radioactive element characterization in environmental samples, contributing significantly to natural and anthropogenic radioactivity evaluations, particularly in areas such as natural reservations or regions that have been affected by nuclear pollutants. As the Danube Delta belongs to both categories, we decided to conduct a study in order to find out whether gamma spectroscopy is suited for pattern identification in common biota constituents such as reed and whether anthropogenic tracers can still be found in the samples. The answer to both questions is affirmative, as shown by the pattern and cluster analyses. Furthermore, our conclusions point out that it would be interesting to extend the spectroscopy and correlation studies to sediment and trophic chains over a certain period in order to obtain the transfer factors and information on radionuclide dynamics. The HPGe detector used proves this is the best class of sensing devices for such purposes. Full article

Auger electrons are low-energy, high-linear-energy-transfer particles that deposit their energy over nanometers distances. Their biological impact depends heavily on where the radionuclide is localized within the cell. To verify the hypothesis that the cell membrane may be a better molecular target than the cytoplasm in Auger electron therapy, we investigated whether the radiotoxicity of ^99mTc varied depending on its location in the cell. The behavior of peptide radiopharmaceuticals ^99mTc-TECANT-1 targeted the cell membrane was compared with ^99mTc-TEKTROTYD directed to the cytoplasm. Our findings confirmed that ^99mTc-TECANT-1 displayed greater binding to AR-42-J cells than ^99mTc-TEKTROTYD. Additionally, it was demonstrated that the receptor agonist ^99mTc-TEKTROTYD is localized in more than 90% of the cytoplasm, while ^99mTc-TECANT-1 is found in 60–80% of the cell membrane. When evaluating cell survival using the MTS assay, we observed that toxicity was significantly higher when ^99mTc was targeted to the membrane compared to the cytoplasm. This indicates that, for ^99mTc, as with ¹⁶¹Tb, the membrane is a more sensitive target for Auger electrons than the cytoplasm. Our results also suggest that receptor antagonists labelled with therapeutic doses of ^99mTc may be effective in treating certain cancers. However, further detailed studies, particularly dosimetric investigations, are necessary to validate these findings. Full article

The radiological impact of radionuclide transport via groundwater pathways at the Wolsong Low- and Intermediate-Level Waste (LILW) Disposal Center was estimated by considering site-specific characteristics, including hydrogeology, geochemistry, and land use. Human intrusion scenarios, such as groundwater well development, were analyzed to evaluate potential pumping volumes and radionuclide migration pathways. Particular attention was given to the hydrological and geochemical aspects of radionuclide transport, with a focus on local aquifer heterogeneity, flow dynamics, and interactions with engineered barriers and surrounding rock formations that delay radionuclide migration through sorption and other retention mechanisms. Sorption coefficients (K_d), calibrated using site-specific geochemical data, were incorporated to ensure realistic modeling of radionuclide behavior. A hierarchical approach integrating scenario screening, particle tracking techniques, and mass transfer modeling was employed. Numerical simulations using FEFLOW ver. 7.3 and GoldSim ver. 14.0 software provided insights into near-field and far-field transport phenomena under well pumping conditions. The results revealed distinct spatial flux behaviors, where carbon-14 (¹⁴C) dominated near-field flux due to its high inventory, while technetium-99 (⁹⁹Tc) emerged as the primary dose contributor in the far-field flux, owing to its anionic nature and limited sorption capacity. Additionally, under high-pH conditions near concrete barriers, cellulose degradation into isosaccharinic acid was identified, enhancing radionuclide mobility through complex formation. These findings underscore the importance of site-specific sorption and speciation parameters in safety assessment and highlight the need for accurate geochemical modeling to optimize waste placement and ensure long-term disposal safety. The outcomes provide valuable insights for optimizing waste placement and contribute to the development of evidence-based safety strategies for long-term performance assessment. Full article

This study analyzed the activity concentrations of various radionuclides in irrigation water, rice components, and corresponding soil samples from eleven paddy fields, revealing significant findings with potential environmental and health implications. The soil exhibited high levels of activity concentrations ranging from 350 to 829, 12.4 to 41.2, and 18.5 to 60.3 Bq/kg, with mean values of 609, 31.1, and 45.0 Bq/kg for ⁴⁰K, ²²⁶Ra, and ²³²Th respectively. Additionally, 12 soil samples from two paddy fields showed ¹³⁷Cs activity concentrations of 5.6 ± 1.3 Bq/kg. The rice plant roots accumulated the highest percentages of total activity concentrations for ²²⁶Ra, ²³²Th, and ¹³⁷Cs, ranging from 76–86%, while only 1.1–10.0% were found in the un-hulled grain. For ⁴⁰K, activity concentrations were distributed among the root (23%), stem (32%), leaf (35%), and un-hulled grain (10%). The mean activity concentrations were 99 ± 12, 0.49 ± 0.09, 0.43 ± 0.12, and 0.10–0.31 Bq/kg for ⁴⁰K, ²²⁶Ra, ²³²Th, and ¹³⁷Cs for un-hulled rice grain, respectively. Transfer factors (TFs) from soil to un-hulled rice grain were calculated as (1.21–2.86) × 10⁻¹ for ⁴⁰K, (0.07–0.11) × 10⁻¹ for ²³²Th, (0.11–0.29) × 10⁻¹ for ²²⁶Ra, and (0.16–0.61) × 10⁻¹ for ¹³⁷Cs. Notably, significant negative correlations were observed between TFs and soil concentrations for ⁴⁰K (r = 0.92, p < 0.001, n = 11) and ²²⁶Ra (r = 0.98, p = 0.026, n = 4), suggesting that macronutrients in soil solutions may inhibit the linear transfer of natural nuclides from the soil solution to rice plants. Full article

The Boda Claystone Formation (BCF) is considered to serve as a natural barrier to the potential high-level radioactive waste repository in Hungary. In order to evaluate the radionuclide retention capacity of the albitic claystone of the BCF, the adsorption and diffusion properties of the rock for Ni²⁺ and Co²⁺ cations (activation products) were investigated separately and in competitive conditions when the two ions were simultaneously added. Batch sorption experiments were performed with powdered and conditioned albitic claystone samples in synthetic pore water to obtain adsorption isotherms. In addition, adsorption tests were performed on petrographic thin sections to check the transferability between dispersed and compact systems. Correlation analysis of microscopic X-ray fluorescence elemental maps recorded on thin sections suggested that nickel is primarily bound to clay minerals (mainly illite and chlorite), which was confirmed by (scanning) transmission electron microscopy measurements. Around illite particles, a newly formed nickel-rich few atomic layer thick phyllosilicate phase was identified. The discrepancy between the experimental and modeled adsorption isotherm at high concentrations could be explained with this nickel-rich new phase. Apart from C_in = 10⁻³ M and only Ni²⁺ or Co²⁺ in the source, the apparent diffusion coefficients of Ni²⁺ and Co²⁺ (C_in = 10⁻³–10⁻² M) were found to be similar. Overall, the BCF shows promising capabilities to retain the studied radionuclides. Full article