Search Results (1,507)

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article

Some of nuclear power’s primary detractors are the unique environmental challenges and impacts of radioactive wastes generated during fuel cycle operations. Key benefits of spent fuel reprocessing (SFR) are reductions in primary high active waste (HAW) masses, volumes, and lengths of radiotoxicity at the expense of secondary waste generation and high capital and operational costs. By employing advanced waste management and resource recovery concepts in SFR beyond the existing standard PUREX process, such as minor actinide and fission product partitioning, these challenges could be mitigated, alongside further reductions in HAW volumes, masses, and duration of radiotoxicity. This work assesses various current and proposed SFR and fuel cycle options as base cases, with further options for fission product partitioning of the high heat radionuclides (HHRs), rare earths, and platinum group metals investigated. A focus on primary waste outputs and the additional energy that could be generated by the reprocessing of high-burnup PWR fuel from Gen III(+) reactors using a simple fuel cycle model is used; the effects of 5- and 10-year spent fuel cooling times before reprocessing are explored. We demonstrate that longer cooling times are preferable in all cases except where short-lived isotope recovery may be desired, and that the partitioning of high-heat fission products (Cs and Sr) could allow for the reclassification of traditional raffinates to intermediate level waste. Highly active waste volume reductions approaching 50% vs. PUREX raffinate could be achieved in single-target partitioning of the inactive and low-activity rare earth elements, and the need for geological disposal could potentially be mitigated completely if HHRs are separated and utilised. 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

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

This study evaluated the activity concentrations of radionuclides in honey, bee pollen, bee bread, and propolis from multiple regions in Poland (Europe) to assess the levels of radiological contamination and their implications for public health. Furthermore, the work considers the use of bee products as bioindicators of the state of environmental contamination with radionuclides. The apiaries from which the samples were collected were selected in eight provinces in Poland, and are also complemented by reference data from soil contamination monitoring. Radionuclide measurements included both natural (e.g., ⁴⁰K, ²²⁶Ra) and anthropogenic isotopes (e.g., ¹³⁷Cs). The results show that although the overall activity concentrations were generally low, certain locations exhibited elevated levels of ¹³⁷Cs in bee products, likely reflecting historical deposition in soils. Propolis was best correlated with ¹³⁷Cs deposited in soil compared to the other products studied. The patterns observed substantiate the hypothesis that bee products, predominantly propolis, accurately reflect local radiological conditions, thereby providing a practical and non-intrusive approach to monitoring radionuclide contamination and informing risk management strategies. An assessment of potential health risks indicates that the effective dose is safe and ranges from 0.02 to 10.3 µSv per year, depending on the type of product and consumption. Full article

Bis(2-ethylhexyl) phosphate (P204) is widely used in extraction processes in the nuclear and rare earth industries. However, its high solubility in water results in high levels of total organic carbon and phosphorus in aqueous environments, and may also lead to radioactive contamination when it is used to combine with radionuclides. In this paper, we characterized a coconut shell activated carbon (CSAC) and a coal-based activated carbon (CBAC) for the adsorption of P204 and then evaluated their adsorption performance through batch and column experiments. The results found that, except for the main carbon matrix, CSAC and CBAC carried rich oxygen-containing functional groups and a small amount of inorganic substances. Both adsorbents had porous structures with pore diameters less than 4 nm. CSAC and CBAC showed good removal performance for P204 under low pH conditions, with removal efficiencies significantly higher than those of commonly used adsorption resins (XAD-4 and IRA900). The adsorption kinetics of P204 conformed to the pseudo-second-order kinetic model, and the adsorption isotherms conformed to the Langmuir model, indicating a monolayer chemical reaction mechanism. Both adsorbents exhibited strong anti-interference capabilities; their adsorption performance for P204 did not change greatly with the ambient temperature or the concentrations of common interfering ions. Column experiments demonstrated that CSAC could effectively fix dissolved P204 with a removal efficiency exceeding 90%. The fixed P204 could be desorbed with acetone. The findings provide an effective method for the recovery of P204 and the regeneration of spent activated carbon, which shows promise for practical applications in the future. Full article

In the decommissioning of nuclear facilities, activated steel often contains radionuclides such as ⁵⁵Fe and ⁶³Ni, which are categorized as hard-to-measure due to their emission of only low-energy beta particles or X-rays. In samples exhibiting very low radioactivity, close to background levels, a large quantity of steel must undergo extensive physical and chemical processing to achieve the Minimum Detectable Activity Concentration (MDC) necessary for clearance, recycling, or reuse. Italian regulations set particularly stringent clearance levels for these radionuclides (1 Bq/g for both ⁵⁵Fe and ⁶³Ni), significantly lower than those specified in the EU Directive 2013/59 (1000 Bq/g for ⁵⁵Fe and 100 Bq/g for ⁶³Ni). Additionally, Italian authorities may enforce even stricter limits depending on specific circumstances. The analytical challenge is compounded by the presence of large amounts of non-radioactive Fe and Ni, which can cause color quenching, further extending analysis times. This study presents a reliable and optimized method for the quantitative determination of ⁵⁵Fe and ⁶³Ni in steel samples with activity levels approaching regulatory thresholds. The methodology was specifically developed and applied to steel from the Frascati Tokamak Upgrade (FTU) facility, under decommissioning by ENEA. The optimization process demonstrated that achieving the required MDCs necessitates acquisition times of approximately 5 days for ⁵⁵Fe and 6 h for ⁶³Ni, ensuring compliance with stringent regulatory requirements and supporting efficient laboratory workflows. Full article

Background and Objectives: Peptide receptor radionuclide therapy (PRRT) using radiopharmaceuticals labelled with Lutetium-177 is currently a therapeutic option for patients with advanced neuroendocrine neoplasms overexpressing somatostatin receptors (SSTRs). One promising option that has gained interest for PRRT is using alpha-emitting radioisotopes such as Actinium-225. The aim of this study was to perform a systematic review and meta-analysis on the efficacy and safety of radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms. Materials and Methods: A comprehensive literature search of studies on radioligand therapy with Actinium-225 DOTATATE in neuroendocrine neoplasms was carried out. Three different bibliographic databases (Cochrane Library, Embase, and PubMed/MEDLINE) were screened up to May 2025. Eligible articles were selected, relevant data were extracted, and the main findings on efficacy and safety are summarized through a systematic review. Furthermore, proportional meta-analyses on the disease response rate and disease control rate were performed. Results: Five studies (153 patients) published from 2020 were included in the systematic review. The pooled disease response rate and disease control rate of radioligand therapy using Actinium-225 DOTATATE were 51.6% and 88%, respectively. This treatment was well-tolerated in most patients with advanced, metastatic or inoperable neuroendocrine neoplasms. Conclusions: Radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms is effective with an acceptable toxicity profile and potential advantages compared with SSTR-ligands labelled with Lutetium-177. Currently, the number of published studies on this treatment is still limited, and results from multicenter randomized controlled trials are needed to translate this therapeutic option into clinical practice. Full article

When non-functioning pituitary adenomas (NFPAs) behave aggressively or recur after first-line surgical treatment, it can be challenging to decide whether and how to escalate therapy. Up to 47% of patients with residual tumor after transsphenoidal surgery will show disease recurrence or progression and may require an intervention. Repeat surgical resection can be attempted in select cases if the tumor is accessible; for the remainder of patients, non-surgical treatment options may need to be considered. Radiotherapy can control tumor growth in 75% of NFPAs, but confers increased risk of hypopituitarism and other disorders. Currently, there are no medical therapies approved for patients with recurrent or aggressive NFPA. However, several have been investigated, including temozolomide, somatostatin receptor ligands, dopamine agonists, immune checkpoint inhibitors, vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. We present a review of the available evidence to provide guidance for pituitary endocrinologists and neuro-oncologists when treating patients with recurrent or aggressive NFPA. Full article

Between approximately 725 and 518 Ma, a suite of specialized felsic plutons and granitic stocks were emplaced across the Arabian Shield, many of which are now recognized as highly mineralized prospects enriched in rare earth elements (REEs), rare metals, and radioactive elements bearing mineralizations. The current investigation focused on the radiological and geochemical characterization of naturally occurring radionuclides, specifically ²³⁸U, ²²⁶Ra, ²³²Th, and ⁴⁰K, within three strategically selected granitic prospects, namely, J. Tawlah albite granite (TW), J. Hamra (HM), and J. Abu Al Dod alkali feldspar syenite and granites (AD). Concerning the radioactivity levels of the investigated granitic stocks, specifically the activity concentrations of ²³⁸U, ²²⁶Ra, ²³²Th, and ⁴⁰K, the measured average values demonstrate significant variability across the TW, HM, and AD stocks. The average ²³⁸U concentrations are 195 (SD = 38.7), 88.66 (SD = 25.6), and 214.3 (SD = 140.8) Bq/kg for TW, HM, and AD granitic stocks, respectively. Corresponding ²²⁶Ra levels are recorded at 172.4 (SD = 34.6), 75.62 (SD = 25.9), and 198.4 (SD = 139.5) Bq/kg. For ²³²Th, the concentrations are markedly elevated in TW at 5453.8 (SD = 2182.9) Bq/kg, compared to 77.16 (SD = 27.02) and 160.2 (SD = 103.8) Bq/kg in HM and AD granitic stocks, respectively. Meanwhile, ⁴⁰K levels are reported at 1670 (SD = 535.9), 2846.2 (SD = 249.9), and 3225 (SD = 222.3) Bq/kg for TW, HM, and AD granitic plutons, respectively. Notably, these values exceed the global average background levels, indicating an anomalous enrichment of the studied granitic occurrences. The mean radiological hazard indices for each granitic unit generally exceed global benchmarks, except for AEDE_out in the HM and AD stocks, which remain below international limits. The geochemical disparities observed are indicative of post-magmatic alteration processes, as substantiated by the interpretation of remote sensing datasets. In light of the significant radiological burden presented by these granitic stocks, it is essential to implement a rigorous precautionary framework for any future mining. These materials must be categorically excluded from uses that entail direct human exposure, especially in residential construction or infrastructure projects. Full article

Targeted radionuclide therapy (TRT) utilizes radiopharmaceuticals to deliver radiation directly to cancer cells while sparing healthy tissues. Beyond the absorbed dose of ablative radiation, TRT induces non-targeted effects (NTEs) that significantly enhance its therapeutic efficacy. These effects include radiation-induced bystander effects (RIBEs), abscopal effects (AEs), radiation-induced genomic instability (RIGI), and adaptive responses, which collectively influence the behavior of cancer cells and the tumor microenvironment (TME). TRT also modulates immune responses, promoting immune-mediated cell death and enhancing the efficacy of combination therapies, such as the use of immune checkpoint inhibitors. The molecular mechanisms underlying TRT involve DNA damage, oxidative stress, and apoptosis, with repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ) playing critical roles. However, challenges such as tumor heterogeneity, hypoxia, and radioresistance limit the effectiveness of this approach. Advances in theranostics, which integrate diagnostic imaging with TRT, have enabled personalized treatment approaches, while artificial intelligence and improved dosimetry offer potential for treatment optimization. Despite the significant survival benefits of TRT in prostate cancer and neuroendocrine tumors, 30–40% of patients remain unresponsive, which highlights the need for further research into molecular pathways, long-term effects, and combined therapies. This review outlines the dual mechanisms of TRT, direct toxicity and NTEs, and discusses strategies to enhance its efficacy and expand its use in oncology. Full article

Zirconium-89 (⁸⁹Zr) is a widely used radionuclide in immune-PET imaging due to its physical decay characteristics. Despite its importance, the production of ⁸⁹Zr radiopharmaceuticals remains largely manual, with limited cost-effective automation solutions available. To address this, we developed an automated system for the agile and reliable production of radiopharmaceuticals. The system performs transmutations, dissolution, and separation for a range of radioisotopes. Steps in the production of ⁸⁹Zr-oxalate are used as an exemplar to illustrate its use. Three-dimensional (3D) printing was exploited to design and manufacture a target holder able to include solid targets, in this case an ⁸⁹Y foil. Spot welding was used to attach ⁸⁹Y to a refractory tantalum (Ta) substrate. A commercially available CPU chiller was repurposed to efficiently cool the metal target. Furthermore, a commercial resin (ZR Resin) and compact peristaltic pumps were employed in a compact (10 × 10 × 10 cm³) chemical separation unit that operates automatically via computer-controlled software. Additionally, a standalone 3D-printed unit was designed with three automated functionalities: photolabelling, vortex mixing, and controlled heating. All components of the assembly, except for the target holder, are housed inside a commercially available hot cell, ensuring safe and efficient operation in a controlled environment. This paper details the design, construction, and modelling of the entire assembly, emphasising its innovative integration and operational efficiency for widespread radiopharmaceutical automation. 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