Search Results (299)

This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-223 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Actinium-225 is the most widely studied alpha emitter, with several preclinical and clinical studies on prostate cancer and neuroendocrine tumours. Other types of tumours (such as glioblastoma) still require preclinical and clinical development. Bismuth-213 bound to antibodies, peptides and nanobodies has shown optimal results in preclinical and clinical studies, with increased median survival and no significant toxicity. Astatine-211 differs from most other α-emitters relevant to TAT, since it yields one α-particle per decay. This offers certain translational advantages, including the simplification of radiation dosimetry calculations and quality control (QC). Lead-212 has the advantage of being an in situ generator with likely widespread availability. Although clinical data are limited, the findings are promising at this stage. The unconventional production of Terbium-149 is the primary reason it has not yet progressed to clinical trials. Overcoming this production obstacle would allow more detailed preclinical investigations. Optimal results with Thorium-227-labelled agents have been observed in preclinical studies, including delays in cellular growth, multiple double-strand breaks and complete regression. Intermediate phase I trial results have also been reported, demonstrating safety and tolerability, as well as an objective response rate of 25%.: The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, as well as suggesting that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges. Full article

Groundwater quality is a key factor and a critical determinant of public health, agriculture, and socio-economic development, particularly in regions where private wells and mineral springs constitute the primary water sources. This study presents an integrated hydrochemical, radiological, and toxicological assessment of groundwater in the Sângeorz-Băi area, Romania, a spa region where mineral waters hold both therapeutic and economic significance. Samples from mineral springs, the municipal supply system, and private wells were analyzed to evaluate compliance with national and international standards and to assess their suitability for drinking, therapeutic, and agricultural purposes. The results reveal distinct hydrochemical contrasts between sources. Mineral springs are characterized by elevated salinity, hardness, and Na–HCO₃ facies, whereas the municipal network and private wells are dominated by Ca–HCO₃ facies. More than half of the private wells exceeded permissible limits for NO₃⁻, NO₂⁻, NH₄⁺, Pb, and Fe, with one well posing a significant nitrite-related health risk. Trace metal analysis indicated localized enrichment in Cu, Fe, and Pb. Radon and radium activities generally complied with regulations, although radium occasionally exceeded the more stringent WHO guidelines. Seasonal variation was minimal, reflecting stable groundwater chemistry. Health risk and irrigation assessments suggest that municipal supply water is largely safe for consumption, while private wells require targeted monitoring and mitigation. Despite elevated Na⁺ and Cl⁻, mineral springs retain therapeutic value under controlled use. This study provides a replicable framework for groundwater quality assessment in spa regions and offers critical insights for public health protection, sustainable tourism, and agricultural resilience. Full article

This study examines the impact of physicochemical and geological factors on radon concentrations in groundwater throughout the Mexican Altiplano. Geological diversity, uranium deposits, seismic zones, and geothermal areas with high heat flow are all potential factors contributing to the presence of radon in groundwater. To move beyond local-scale assessments, this research employs spatial prediction methodologies that incorporate geological and geochemical variables recognized for their role in radon transport and geogenic potential. Certain properties of radon enable it to serve as an ideal tracer, viz., short half-life, inertness, and higher incidence in groundwater than surface water. Twenty-five variables were analyzed in samples from 135 water wells. Geostatistical techniques, including inverse distance weighted interpolation and kriging, were used in conjunction with multivariate statistical analyses. Salinity and geothermal heat flow are key indicators for determining groundwater origin, revealing a dynamic interplay between geothermal activity and hydrogeochemical evolution, where high temperatures do not necessarily correlate with increased solute concentrations. The occurrence of toxic trace elements such as Cd, Cr, and Pb is primarily governed by lithogenic sources and proximity to mineralized zones. Radon levels in groundwater are mainly influenced by geological and structural features, notably rhyolitic formations and deep hydrothermal systems. These findings underscore the importance of site-specific groundwater examination, combined with spatiotemporal models, to account for uranium–radium dynamics and flow paths, thereby enhancing radiological risk assessment. Full article

This study provides a comprehensive evaluation of naturally occurring radionuclides—radium-226 (²²⁶Ra), thorium-232 (²³²Th), and potassium-40 (⁴⁰K)—in groundwater systems across the Nile Valley regions of Upper Egypt, based on the analysis of 85 groundwater wells. Measured mean activity concentrations were 0.74 ± 0.3 Bq/L for ²²⁶Ra, 0.24 ± 0.1 Bq/L for ²³²Th, and 13 ± 4 Bq/L for ⁴⁰K, with ²²⁶Ra displaying low correlations with salinity indicators including chloride (Cl⁻), sodium (Na⁺), electrical conductivity (EC), and total dissolved solids (TDS). Notably, approximately 30% of sampled wells exceeded the World Health Organization (WHO) guidance level of 1 Bq/L for ²²⁶Ra, primarily in central and eastern zones influenced by elevated salinity and evaporite dissolution processes. Geospatial mapping combined with multivariate statistical analysis identified four principal components accounting for over 85% of total data variability, demonstrating that depth-dependent processes, including prolonged water–rock interaction and redox evolution, are the primary controls on ²²⁶Ra mobilization, with salinity-driven ion exchange as a secondary factor. Minor anthropogenic influences, potentially linked to agricultural activities in shallow aquifers, were also detected. Radiological risk assessment confirmed that calculated annual effective doses remain well within international safety limits (<1 mSv/year), although infants and children demonstrated relatively higher exposure levels due to increased water intake per unit body weight. Lifetime cancer risk estimates via ingestion pathways yielded values below 1 × 10⁻⁴, aligning with global health organization benchmarks and reinforcing the general safety of groundwater use in the region. The study highlights potential risks posed by saline groundwater to ancient monuments and archaeological sites, as the cycles of salt forming and breaking down might speed up damage to buildings made of limestone and sandstone. These findings establish a robust scientific foundation for future groundwater quality management and cultural heritage conservation efforts in the Nile Valley region of southern Egypt. Full article

Natural radionuclides may occur in groundwater and pose health risks when present in elevated concentrations. This study evaluates the quality of shallow groundwater in Nysa County (SW Poland) based on the activity concentrations of natural radionuclides radon (²²²Rn) and radium (²²⁶Ra) and estimates the associated radiological risk from water ingestion. Twenty-three groundwater samples were collected from private wells located within two distinct geological units: the Fore-Sudetic Block and the Opole Trough. Activity concentrations of ²²²Rn and ²²⁶Ra were measured using the liquid scintillation counting method. A spatial distribution model for ²²²Rn was developed using inverse distance weighting in QGIS. Local hydrogeochemical background levels were determined using the Q-Dixon test, interquartile range, and Shapiro–Wilk normality test. The background ranged from 2.6 to 3.9 Bq·L⁻¹ in the Opole Trough and from 0 to 10.7 Bq·L⁻¹ in the Fore-Sudetic Block. The lower detection limit (0.05 Bq·L⁻¹) for ²²⁶Ra activity concentration measurements was not exceeded. Effective dose rates were calculated in accordance with the recommendations of the International Commission on Radiological Protection and United Nations Scientific Committee on the Effects of Atomic Radiation. Doses ranged from <1 µSv to over 120 µSv·y⁻¹. Although all samples met national regulatory standards (≤1 mSv·y⁻¹), the World Health Organization reference level (0.1 mSv·y⁻¹) was exceeded in two cases. The results support the need for the radiological monitoring of unregulated private wells and provide a scientific basis for the refinement of legal frameworks and health protection strategies. Full article

Brazil nuts (Bertholletia excelsa), mainly from the Amazon, are notable for their exceptionally high selenium (Se) content and are widely consumed as a natural dietary supplement. They also contain potentially harmful elements, including barium (Ba), and exhibit an unusual capacity to accumulate radioactive radium (Ra). In this study, we quantified the concentrations of Se, Ba, strontium (Sr), lanthanum (La), europium (Eu), and the radionuclides ²²⁶Ra and ²²⁸Ra, and assessed their in vitro bioaccessibility—data largely unavailable for these elements to date. Se was highly bioaccessible (≈85%), whereas Ba and Ra, both chemo- and/or radiotoxic, exhibited low bioaccessibility (≈2% each). Nuclear magnetic resonance (NMR) spectroscopy revealed Se to occur predominantly as selenomethionine (SeMet), alongside phytate, amino acids, peptides, and other polar low-molecular-weight compounds. The influence of Brazil nut flour (BNF) on Eu(III) speciation in simulated gastrointestinal fluids, and the effect of chelating agents such as ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and the hydroxypyridinone 3,4,3-LI(1,2-HOPO) were investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS). Results indicate that the food matrix has only a minor impact on the decorporation efficacy of these chelators. These findings provide novel insights into the bioaccessibility and chemical speciation of nutritionally and toxicologically relevant elements in Brazil nuts. Full article

Background/Objectives: In patients with metastatic castration-resistant prostate cancer (mCRPC) and osseous metastases only, ²²³Radium therapy represents a valuable therapeutic option. Bone scintigraphy (BS) is typically performed to assess metastasis load, with the BS-derived automated bone scan index (aBSI) used for response assessment. This study aimed to evaluate the prognostic value of aBSI in patients receiving three or six cycles of ²²³Ra therapy. Methods: We included patients that were diagnosed with extensive osseous tumor load on BS, had no visceral or nodal metastases, had undergone ²²³Ra therapy. The aBSI prior to and following three or six cycles of therapy, total tumor volume (TTV), SUV_max, and overall survival were analyzed. Results: This study included 49 mCRPC patients (mean age: 70 ± 9 years) with 42 (85.7%) receiving six and 7 (14.3%) receiving three cycles. After three cycles, the mean aBSI (p = 0.369), TTV (p = 0.902), and SUV_max (p = 0.149) remained unchanged. After six cycles, the mean aBSI (p = 0.247) and TTV (p = 0.784) were unchanged, while SUV_max decreased significantly (p = 0.001). The aBSI did not significantly correlate with the mean aBSI (six cycles: χ² = 1.823, p = 0.177; three cycles: χ² = 0.308, p = 0.579). Conclusions: Although quantitative changes in TTV and aBSI did not significantly correlate with each other, their respective absolute values consistently indicated stable disease burden under therapy. This highlights its potential as a useful tool for monitoring disease burden while indicating that aBSI alone is insufficient for predicting overall survival. Full article

The drilling core sampling and chemical analysis method for the quantitative determination of solid mineral deposits has several drawbacks, including a low core drilling efficiency, a high core sampling cost, and a long chemical analysis cycle. In current uranium quantification practices, advanced techniques have been developed to preliminarily determine the formation of uranium content based on the interpretation results of natural $\gamma$-ray total logging. However, such methods still require supplementary core chemical analysis to derive the uranium–radium–radon balance coefficient, which is then used for equilibrium correction to obtain the true uranium content within the uranium-bearing layer. Furthermore, conventional prompt neutron time spectrum logging is constrained by low count rates, resulting in slow logging speeds that fail to meet the demands of practical engineering applications. To address this, this study proposes a uranium quantification method that corrects the natural $\gamma$-ray total logging using prompt neutron time spectrum logging. Additionally, a calibration parameter determination method necessary for quantitative interpretation is constructed. Experimental results from standardized model wells indicate that, in sandstone-type uranium deposits, the absolute error of uranium content is within $\pm 0.002\%\mathrm{eU}$, and the relative error is within $\pm 2.5\%$. These findings validate the feasibility of deriving the uranium–radium–radon balance coefficient without relying on core chemical analysis. Compared with the prompt neutron time spectrum logging method, the proposed approach significantly improves the logging speed while producing results that are essentially consistent with those of natural $\gamma$-ray total logging. It provides an efficient and accurate solution for uranium quantitative interpretation. Full article

Prostate cancer is the second leading cause of cancer-related death in men, with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases representing a critical clinical challenge. Although radium-223 (Ra-223) is approved for treating mCRPC with bone metastases, its efficacy remains limited, necessitating the development of more effective therapies. This study investigates the therapeutic potential of ¹⁷⁷Lu-PSMA-617, a PSMA-targeted radiopharmaceutical, in a murine model of prostate cancer bone metastases. To our knowledge, this is the first study to systematically evaluate ¹⁷⁷Lu-PSMA-617 in an orthotopic bone metastatic prostate cancer model, providing a clinically relevant preclinical platform to assess both imaging and therapeutic performance. We conducted comprehensive preclinical evaluations, including synthesis, stability analysis, cell binding assays, nuclear imaging, in vivo biodistribution, pharmacokinetics, and antitumor efficacy. The synthesis of ¹⁷⁷Lu-PSMA-617 demonstrated high radiochemical yield (99.2%), molar activity (25.5 GBq/μmol), and purity (>98%), indicating high product quality. Stability studies confirmed minimal release of free Lutetium-177, maintaining the compound’s integrity under physiological conditions. In vitro assays showed selective binding and internalization in PSMA-positive LNCaP prostate cancer cells, with negligible uptake in PSMA-negative PC-3 cells. In vivo biodistribution studies demonstrated efficient tumor targeting, with peak uptake in LNCaP tumors (23.31 ± 0.94 %IA/g) at 4 h post-injection. The radiopharmaceutical exhibited favorable pharmacokinetics, with high tumor-to-background ratios (tumor-to-blood, 434.4; tumor-to-muscle, 857.4). Therapeutic efficacy was confirmed by significant survival extension in treated mice (30.7% for 37 MBq and 53.8% for 111 MBq), with median survival times of 34 and 40 days, respectively, compared to 26 days in the control group. Radiation dosimetry analysis indicated a favorable safety profile with a calculated effective dose of 0.127 mSv/MBq. These findings highlight the novelty and translational relevance of using ¹⁷⁷Lu-PSMA-617 in a clinically relevant bone metastasis model, reinforcing its potential as a dual-purpose agent for both targeted therapy and molecular imaging in advanced prostate cancer. Full article

The combustion of hard coal and lignite in power and combined heat and power plants generates significant amounts of coal fly ash (CFA), a waste material with variable properties. CFA naturally contains radionuclides, specifically naturally occurring radioactive materials (NORMs), which pose potential radiological risks to the environment and human health during their storage and utilization, including their incorporation into building materials. Although global research on the radionuclide content in CFA is available, there is a clear gap in detailed and current data specific to Central and Eastern Europe and notably, a lack of a systematic analysis investigating the influence of installed power plant capacity on the concentration profile of these radionuclides in the generated ash. This study aimed to fill this gap and provide crucial data for the Polish energy and environmental context. The objective was to evaluate the concentrations of selected radionuclides (²³²Th, ²²⁶Ra, and ⁴⁰K) in coal fly ash samples collected between 2020 and 2023 from 19 Polish power and combined heat and power plants with varying capacities (categorized into four groups: S1–S4) and to assess the associated radiological risk. Radionuclide concentrations were determined using gamma spectrometry, and differences between groups were analyzed using non-parametric statistical methods, including PERMANOVA. The results demonstrated that plant capacity has a statistically significant influence on the concentration profiles of thorium and potassium but not radium. Calculated radiological hazard assessment factors (Ra_eq, H_ex, H_in, IAED) revealed that although most samples fall near regulatory limits (e.g., 370 Bq kg⁻¹ for Ra_eq), some exceed these limits, particularly in groups S1 (plants with a capacity less than 300 MW) and S4 (plants with a capacity higher than 300 MW). It was also found that the frequency of exceeding the annual effective dose limits (IAEDs) showed an increasing trend with the increasing installed capacity of the facility. These findings underscore the importance of plant capacity as a key factor to consider in the radiological risk assessment associated with coal fly ash. This study’s outcomes are crucial for informing environmental risk management strategies, guiding safe waste processing practices, and shaping environmental policies within the energy sector in Central and Eastern European countries, including Poland. Full article

Introduction: Prostate cancer has been generally resistant to immunotherapy approaches. Radiation can be immunostimulatory, but the extent to which standard prostate cancer treatments induce immune activation has not been well described. The bone-targeted radiopharmaceutical Radium223 (Ra223) has been proposed to enrich immune function, but clinical studies have not fully delineated whether this is true, or by what mechanisms. Enzalutamide has been shown to increase PD-L1 expression on dendritic cells, which could impact immune activation, though the extent to which this is associated with other evidence of immune activation remains uncertain, and combination strategies remain of interest. We performed a randomized phase II trial to evaluate whether Radium223 (Ra223) added to enzalutamide would induce greater immune activation and clinical responses compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Eligible patients were randomized 2:1 to Arm A (enzalutamide 160 mg PO daily + Ra223 55 kBq/kg IV q4 weeks × 6 doses) or Arm B (enzalutamide 160 mg PO daily). Blood was collected at treatment start and during treatment to measure soluble immune checkpoint biomarkers (BTLA, TIM3, HVEM, GITR, LAG3, PD-1, CTLA-4, PD-L1, PD-L2, ICOS). Immunophenotyping by mass cytometry time of flight (CyTOF) was performed to measure peripheral blood mononuclear cell populations before and after treatment. CyTOF was used to determine changes in circulating immune cell population subsets before and after treatment. Biopsies were performed of an active bone metastatic lesion prior to study treatment and after at least 3 months. IHC was subsequently performed to examine changes in immune cell population subsets before and after treatment, and changes in pSTAT3 levels. Results: In total, 30 patients were enrolled, with median age 68. The median duration of follow up was 36 months. PSA responses, PFS, and OS were not significantly different between the two arms; however, the study was not powered for clinical endpoints. Peripheral blood and bone biopsy specimens were analyzed for immune correlatives. Soluble receptor concentrations showed significantly increased expression of PDL-2 in the combination arm, but this was not seen on CyTOF. Otherwise, there were no significant differences in markers of immune activation/exhaustion or immune cell population subsets in the combination arm and enzalutamide monotherapy arm. IHC also did not show a significant difference in immune cell population subsets in bone biopsy specimens before and after treatment in both arms. However, treatment with the combination arm did show significantly increased levels of pSTAT3 (p = 0.04), which was not seen in the enzalutamide monotherapy arm. Conclusions: Our study showed an overall lack of evidence for immune activation or cytokine induction with the combination, which does not make a strong case for combinatorial immunotherapy approaches. However, the combination did induce higher levels of pSTAT3, which has been implicated in radio-resistance. Therefore, the addition of a STAT3 inhibitor to the combination may be of interest to improve efficacy. Full article

This study focused on identifying Th-, Nb-Ta-, Zr-, and REE-bearing minerals with a multivariate statistical approach in alkaline syenite to evaluate their radiological risks, at Nikeiba, Egypt. Through microchemical analyses, by utilizing electron probe microanalysis, horite, microlite, monazite, zircon, columbite, and fergusonite were shown to bear uranium and thorium. These minerals have played an important role in higher radioactive zones in the studied alkaline syenite. REE-minerals comprising bastnäsite, monazite, and fluorite and apatite are well recorded. The total rare earth elements (TREE₂O₃) reveal higher concentrations in bastnäsite than monazite, with averages 74.87 and 63.8 wt%. Ce is considered the most predominant LREE in the analyzed bastnäsite and monazite. The mean values of radionuclide activity concentrations of ²³⁸U, ²³²Th, and ⁴⁰K are 108 ± 20 Bq/kg, 107 ± 9 Bq/kg, and 1255 ± 166 Bq/kg, respectively. Radiological assessments revealed a radium equivalent activity of 357 Bq/kg, below global limits, but an air-absorbed dose rate (166 nGy/h) and annual effective doses (0.81 mSv/y indoors, 0.20 mSv/y outdoors) exceeding safe thresholds. Additionally, the excess lifetime cancer risk (ELCR) was calculated at 0.00071, surpassing the acceptable limit of 0.00029, making these rocks unsafe for construction use. Statistical analyses further underscored the relationships between radionuclide concentrations and associated risks, highlighting the necessity for continuous monitoring and mitigation. Full article

The presence of radionuclides in environmental media, including sediment, is critical in assessing potential health risks due to external gamma radiation. This study investigates the spatial distribution of natural (Ra-226, Th-232, K-40) and artificial (Cs-137) radionuclides in sediment along the Dixcove coastline, Ghana, using High-Purity Germanium (HPGe) gamma-ray spectroscopy. The activity concentrations of Ra-226 ranged from ~14 to ~23 Bq/kg, Th-232 from ~3 to ~10 Bq/kg, and K-40 from ~44 to ~93 Bq/kg, with Cs-137 levels between 0.2 and 1.3 Bq/kg. The highest concentrations of Ra-226 and K-40 were found On-shore, suggesting terrestrial influence, while Th-232 displayed a more uniform distribution. Radiological risk assessments, including radium equivalent activity (Raeq), annual effective dose (AED), and gamma index (Iγ), confirmed that all measured values were below international safety thresholds, indicating no significant health risk. However, the variability in Cs-137 distribution suggests the need for continued monitoring to assess potential long-term contamination trends. A significant discrepancy was observed when comparing Cs-137 values from this study (maximum 1.3 Bq/kg) with previously reported data (~110 Bq/kg), raising concerns about methodological differences or environmental changes, which require further investigation. To address the observed discrepancies between this study and previous investigations, future research should incorporate in situ measurement techniques for a more comprehensive assessment of Cs-137 distribution. Full article

Radium-223 (²²³Ra) was the first radioactive isotope approved for treating castration-resistant prostate cancer (CRPC) with symptomatic bone metastases without visceral metastatic disease. To better understand the action of ²²³Ra, its role in the tumor microenvironment represents a crucial aspect. A literature search was conducted using the PubMed/MEDLINE database and studies regarding the relationship between ²²³Ra and the tumoral microenvironment were considered. The tumoral microenvironment is a complex setting in which complex interactions between cells and molecules occur. Radium-223, as an alpha-emitter, induces double-stranded DNA breaks; to potentiate this effect, it could be used in patients with genetic instability but also in combination with therapies which inhibit DNA repair, modulate the immune response, or control tumor growth. In conclusion, a few studies have taken into consideration the tumoral microenvironment in association with ²²³Ra. However, its understanding is a priority to better comprehend how to effectively exploit ²²³Ra and its action mechanism. Full article

Background/Objectives: The prognostic value of baseline clinical parameters in predicting the survival prolonging effect of Radium-223-dichloride (²²³RaCl₂) for metastatic castration resistant prostate cancer (mCRPC) patients has been the object of intensive research and remains an open issue. This national multicenter study aimed to corroborate the evidence of ten years of clinical experience with ²²³RaCl₂ by collecting data from eight Italian Nuclear Medicine Units. Methods: Data from 581 consecutive mCRPC patients treated with ²²³RaCl₂ were retrospectively analyzed. Several baseline variables relevant to the overall survival (OS) analysis were considered, including age, previous radical prostatectomy/radiotherapy, number of previous treatment lines, prior chemotherapy, Gleason score, presence of lymphoadenopaties, number of bone metastases, concomitant use of bisphosphonates/Denosumab, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), as well as baseline values of hemoglobin (Hb), platelets, Total Alkaline Phosphatase (tALP), Lactate Dehydrogenase (LDH), and Prostate-Specific Antigen (PSA). Data were summarized using descriptive statistics, univariate analysis and multivariate analysis with the Cox model. Results: The median OS time was 14 months (95%CI 12–17 months). At univariate analysis age, the number of previous treatment lines, number of bone metastases, ECOG-PS, presence of lymphadenopathies at the time of enrollment, as well as baseline tALP, PSA, and Hb, were independently associated with OS. After multivariate analysis, the number of previous treatment lines (HR = 1.1670, CI = 1.0095–1.3491, p = 0.0368), the prior chemotherapy (HR = 0.6461, CI = 0.4372–0.9549, p = 0.0284), the presence of lymphadenopathies (HR = 1.5083, CI = 1.1210–2.0296, p = 0.0066), the number of bone metastases (HR = 0.6990, CI = 0.5416–0.9020, p = 0.0059), ECOG-PS (HR = 1.3551, CI = 1.1238–1.6339, p = 0.0015), and baseline values of tALP (HR = 1.0008, CI = 1.0003–1.0013, p = 0.0016) and PSA (HR = 1.0004, CI = 1.0002–1.0006, p = 0.0005) remained statistically significant. Conclusions: In the era of precision medicine and in the landscape of novel therapies for mCRPC, the prognostic stratification of patients undergoing ²²³RaCl₂ has a fundamental role for clinical decision-making, ranging from treatment choice to optimal sequencing and potential associations. This large Italian multicenter study corroborated the prognostic value of several variables, emerging from ten years of clinical experience with ²²³RaCl₂. Full article