Concentrations of radionuclides and trace elements in wetlands.

Environmental risks in wetlands are considered with radionuclides and trace elements to understand pollution accumulation. In this study, we aimed to determine the levels of radiation and heavy metals in water systems and assess pollution configurations. Radionuclides (222Rn, 210Pb and 210Po) and trace elements (Ag, As, Ba, Be, Cd, Co, Cr, Cu, Fe, Li, Mo, Ni, Pb, V and Zn) were measured to evaluate anthropogenic factors. Water pollution in wetlands was indicated by mean concentrations of 66.2 mBq/L for 222Rn, 3 mBq/L for 210Pb, 42 mBq/L for 210Po, 41 ppb for Zn, 37 ppb for Ba, 190 ppb for Fe and 481 ppb for Sr. These pollutants may be related to industrial facilities in Kirklareli city, Türkiye.

Anthropogenic and climatic impacts on historic sediment, carbon, and phosphorus accumulation rates using 210Pbex and 137Cs in a sub-watershed linked to Zarivar Lake, Iran.

To estimate a watershed's response to climate change, it is crucial to understand how human activities and climatic extremes have interacted over time. Over the last century, the Zarivar Lake watershed, Iran, has been subjected to various anthropogenic activates, including deforestation and inappropriate land-management practices alongside the implementation of conservation measures like check dams. To understand the effects of these changes on the magnitude of sediment, organic carbon (OC), and phosphorus supplies in a small sub-watershed connected to the lake over the last century, a lake sediment core was dated using 210Pbex and 137Cs as geochronometers. The average mass accumulation rate (MAR), organic carbon accumulation rates (OCAR), and particulate phosphorus accumulation rates (PPAR) of the sediment core were determined to be 6498 ± 2475, 205 ± 85, and 8.9 ± 3.3 g m-2 year-1, respectively. Between the late 1970s and early 1980s, accumulation rates were significantly higher than their averages at 7940 ± 3120, 220 ± 60, and 12.0 ± 2.8 g m-2 year-1 respectively. During this period, the watershed underwent extensive deforestation (12%) on steep slopes, coinciding with higher mean annual precipitations (more than double). Conversely, after 2009, when check dams were installed in the sub-watershed, the sediment load to the lake became negligible. The results of this research indicate that anthropogenic activities had a pronounced effect on MAR, OCAR, and PPAR, causing them to fluctuate from negligible amounts to values twice the averages over the last century, amplified by climatic factors. These results imply that implementing climate-smart watershed management strategies, such as constructing additional check dams and terraces, reinforcing restrictions on deforestation, and minimum tillage practices, can facilitate protection of lacustrine ecosystems under accelerating climate change conditions.

High precision blood lead radiogenic isotope signatures in a community exposed to Pb contaminated soils and implications for the current Pb exposure of the European population.

Our study provides the most comprehensive dataset for high-precision radiogenic isotopes of lead (Pb) in blood for the western European population. It investigates their potential for elucidating the contribution of soil Pb to blood Pb using a human biomonitoring survey involving 81 adults and 4 children living in the urban area of Liège (Belgium). Soils in the area show moderate (median of 360 mg/kg) to high (95th percentile of 1000 mg/kg) Pb concentrations, due to former metal processing activities. Blood lead levels (BLL) measured in the study population are, on average, quantitatively consistent with a âˆ¼ 20 % increase due to the exposure to Pb from soils, as estimated by a single-compartment biokinetic model. Consistently, its isotopic composition does not represent an endmember that fully accounts for the variability of Blood lead isotope (BLI) compositions measured in the study population. While some individuals show more thorogenic BLI ratios (relatively more enriched in 208Pb), which could be consistent with a greater exposure to local soils and/or by their country of birth, the BLI data mostly follow a trend roughly parallel to the European Standard Lead Pollution (ESLP) line, within the European leaded gasoline field, even two decades after the withdrawal of this source. Differences in BLI are probably associated with factors related to the presence of Pb in dwellings (pipes, paint) and drinking water distribution system, suggesting that the anthropogenic Pb in use, relevant to human exposure, may contain ore components of different origins, including the Australian Pb ore signature.

Tracing the Transport and Residence Times of Atmospheric Microplastics Using Natural Radionuclides.

While atmospheric microplastics are known to be transported over long distances, their residence times and transport processes lack clarity. This study utilized natural radionuclides 7Be, 210Pb, and 210Po to explore the transport of atmospheric microplastics in Tianjin, a coastal city in Northern China. Microplastic concentrations ranged from 0.03 to 0.13 particles m-3 over the course of a year. The proportion of microplastic fragments in winter was significantly higher than that in other seasons, with median microplastic sizes in autumn and winter being larger than those in spring and summer. The atmospheric microplastic surface was rough, exhibiting irregular pores and multiple depressions and cracks. Microplastics experienced vertical mixing with the upper atmosphere in April and August and were influenced by rainfall in July. The residence time of atmospheric particles ranged from 9.47 to 22.85 days throughout the year, with an average of 14.41 days. The peak residence time of atmospheric particulates in November may be correlated with increased 210Po levels from coal consumption. Their prolonged atmospheric presence and rough surface allow microplastics to act as carriers for various chemical pollutants, underscoring the complexity and potential risks associated with their presence in the atmosphere.

Alternatives to 137Cs for 210Pb dating validation in south America and in the Carribean region: Point and diffuse sources.

As today the 137Cs fallout peak, in sediment cores, corresponds only to 25% of its initial concentration, alternatives to the use of 137Cs as a210Pb sediment dating validation tool are proposed. In highly industrialized bays, such as Guanabara Bay in the Rio de Janeiro metropolitan region, several chemical/compounds from the surrounding industry releases may be applied as validation tools. Chromium and copper profiles in a sediment core adequately fit the expected pattern due to the implementation of a chemical plant in 1958, reaching their maximum discharge in 1982 and subsequently decreasing due to the operation of a new wastewater treatment plant. A diffuse source such, as the PCB-based mixture Askarel, was also applied as an alternative validation tool, and the observed concentration profile reproduced the expected behavior, with increasing concentration after the Second World War and a decrease after the ban of this product in 1981. The observed Aroclor 1254 and 1260 mixture chlorination rates fit the most widely distributed PCB-based products in the country.

Activity concentration of indoor radon and its short-lived progeny (218Po, 214Pb, and 214Po) and their effect on atmospheric ionization rate in Sana'a, Yemen.

Exposure to ionizing radiation inside houses, especially radionuclides of radon and its progeny, poses serious health risks that can be exacerbated when inhaled as a result of interaction with human lung tissue. Also, air ionization is mainly due to these radionuclides. Therefore, accurate measurements of radon activity concentrations and its short-lived progeny are required to assess dose and environmental pollution and estimate ionization rates in indoor environments. For this purpose, we employed a previously tested and approved reliable method, following the three-count procedure. This method is based on airborne radon progeny sampling on polycarbonate membrane filters and alpha counting using a passive α-dosimetry technique with CR-39 detectors. The method also relies on a PC-based software we developed for solving mathematical equations and calculating all the necessary physical quantities. In this study, the concentrations of radon and individual short-lived radon progeny were measured in 20 houses in Sana'a, Yemen. Measurement conditions and meteorological variables were considered. The average activity concentrations of 222Rn, Equilibrium-Equivalent Concentration (EEC), 218Po, 214 Pb, and 214Po were 73.1 ± 6.0, 29.2 ± 2.4, 44.4 ± 3.6, 30.5 ± 2.5, and 23.2 ± 1.9 Bq.m-3, respectively. The calculated average unattached fractions f1(218Po), f2(214 Pb), and fp were found to be 0.24, 0.04, and 0.07 % respectively. The annual average values of ion-pair production rate caused by 222Rn and their progeny and air ion concentration, were 27.25 ions.cm-3s-1 and 1829 ions.cm-3 respectively. The annual effective dose was estimated to be 1.93 ± 0.16 mSv.y-1, well lower than the recommended 10 mSv.y-1.

Characterization of natural radioactivity and relative dose due to consumption of edible bivalves inhabiting the Cochin Backwater Lagoon, Kerala, southwestern coast of India.

The study on natural radionuclides in edible bivalves from the Cochin backwater lagoon, Kerala, employing alpha spectrometry, revealed higher concentrations of 210Po and 210Pb compared to 238U and 232Th. The annual committed effective dose (ACED) for the adult coastal population was calculated at a range of 1494.9 to 5783.4 µSv y-1, with 210Po being the predominant contributor, responsible for about 85 % of the dose. This highlighted significant health risks, underscored by a calculated cumulative mortality and morbidity risk range between 5.23 × 10-3 and 2.02 × 10-2. These findings emphasized the need for further research and the development of regulatory measures to mitigate exposure risks.

A review of 210Pb and 210Po in moss.

Among environment contaminants, 210Pb and 210Po have gained significant research attention due to their radioactive toxicity. Moss, with its exceptional adsorption capability for these radionuclides, serves as an indicator for environmental 210Pb and 210Po pollution. The paper reviews a total of 138 articles, summarizing the common methods and analytical results of 210Pb and 210Po research in moss. It elucidates the accumulation characteristics of 210Pb and 210Po in moss, discusses current research challenges, potential solutions, and future prospects in this field. Existing literature indicates limitations in common measurement techniques for 210Pb and 210Po in moss, characterized by high detection limits or lengthy sample processing. The concentration of 210Pb and 210Po within moss display substantial variations across different regions worldwide, ranging from

Determination of 90Sr and 210Pb in food samples by liquid scintillation counting after sequential separation with an extraction chromatographic column.

90Sr and 210Pb are considered to be key radionuclides in internal exposure resulting from dietary intake, however, the established methods employed for their detection are time-comsuming. A method for the sequential separation of 90Sr and 210Pb using a Sr·spec resin by LSC measurement is developed, which is highly suitable for food safety monitoring as its minimal sample requirements. The sequential separation of Sr and Pb from the sample was using 0.05 mol/L HNO3 and 0.05 mol/L C6H5O7(NH4)3. The chemical recoveries of Sr and Pb measured using ICP-OES were 72-83% and 80-88%, respectively. The minimum detectable activities of 90Sr and 210Pb in the food sample were 36.2 mBq/kg and 28.6 mBq/kg, respectively, obtained from a 0.1 kg fresh sample and 300 min counting time. The method was validated using reference materials and compared with other methods. The feasibility of the developed method for other highly complex food matrices needs further investigation.

Assessment of cancer risk and radiological effects from 210Po and 210Pb with consumption of wild medicinal herbal plants.

BACKGROUND: Plants' raw materials can accumulate chemical elements, including radioisotopes, to some extent and reflect the region they grow in. Due to their high environmental content and toxicity, natural radionuclides - polonium 210Po and lead 210Pb are the most dangerous radioisotopes for human health. METHODS: 70 raw medicinal herbal materials from 54 popular wild-growing medicinal plant species, most of them included in the European Pharmacopoeia, were collected across three regions. In 210 samples, the activity concentrations of 210Po and 210Pb were determined, and their radiotoxicity and cancer risk were calculated. RESULTS: The results of 210Po and 210Pb activities measured in herbal raw material were from 0.12 mBq g-1 dry weight in the fruits of the common chestnut (Aesculus hippocastanum) to 19.7 mBq g-1 dw in herb of ground elder (Aegopodium podagraria) for 210Po, while for 210Pb ranged from 0.16 mBq g-1 dw to 34.3 mBq g-1 dw in the same plants. There were statistically significant differences between 210Po and 210Pb content in leaves, herbs, flowers, and fruit. The studies indicated that the estimated annual effective radiation dose from Polish medicinal herbs consumption was low, ranging 0.03-105 µSv from 210Po and 0.02-98.2 µSv from 210Pb, while the risk of cancer morbidity and mortality ranged from 10-5 to 10-9. CONCLUSIONS: Consumption of the tested medicinal herbs is safe from the radiological point of view and, based on the predictions related to the calculated risk of cancer, should not increase the probability of its occurrence.

Recent progresses in analytical method development for 210Pb in environmental and biological samples.

As a decay product of uranium series, 210Pb spreads widely in the nature and imposes strong radiological and chemical toxicity. It is vital to establish reliable and efficient radioanalytical methods for 210Pb determination to support environment and food radioactivity monitoring programs. This article critically reviews analytical methods developed for determining 210Pb in environmental and biological samples, especially new development in recent years. Techniques applied throughout different analytical steps including sample pretreatment, separation, purification, and detection are summarized and their pros and cons are discussed to provide a holistic overview for 210Pb environmental and biological assay.

The presence of radiotoxic 210Po and 210Pb in Ukrainian wild medicinal plants and the assessment of related dose and cancer risk.

Herbal plants are considered natural pharmaceuticals but also accumulate chemical elements and compounds at high levels. 210Po and 210Pb are highly radiotoxic and may cause carcinogenesis due to ionizing radiation. Thirteen of the most popular wild-growing herbaceous plant species, mostly included in the European Pharmacopoeia, were collected across Ukraine. 210Po and 210Pb were determined in the medicinal plants, and their radiotoxicity and cancer risk were calculated. The results of 210Po activities measured in herbal raw material ranged from 2.28 Bq kg-1 dw (where dw is dry weight) in herb of common horsetail (Equisetum arvense L.) collected near Lviv to 37.7 Bq kg-1 dw in leaves of common birch (Betula pendula Roth.) from Rava Ruska. The activity concentrations of 210Pb varied from 0.44 Bq kg-1 dw in leaves of common birch from Starokostyantyniv to 28.4 Bq kg-1 dw in leaves of common birch from Mizhhirya. There were statistically significant differences between 210Po and 210Pb content in flowers, leaves, and aerial portions. The studies indicated that the estimated annual effective radiation dose from Ukrainian herbs consumption was low, ranging 5.00-82.6 µSv from 210Po and 0.56-35.8 µSv from 210Pb, while the cancer morbidity and mortality risk ranged from 10-4 to 10-6. The presented data indicated no radiological risk related to using herbal plant materials.

First measurements of radon-220 diffusion in mice tumors, towards treatment planning in diffusing alpha-emitters radiation therapy.

BACKGROUND: Diffusing alpha-emitters radiation therapy ("Alpha-DaRT") is a new method for treating solid tumors with alpha particles, relying on the release of the short-lived alpha-emitting daughter atoms of radium-224 from interstitial sources inserted into the tumor. Alpha-DaRT tumor dosimetry is governed by the spread of radium's progeny around the source, as described by an approximate framework called the "diffusion-leakage model". The most important model parameters are the diffusion lengths of radon-220 and lead-212, and their estimation is therefore essential for treatment planning. PURPOSE: Previous works have provided initial estimates for the dominant diffusion length, by measuring the activity spread inside mice-borne tumors several days after the insertion of an Alpha-DaRT source. The measurements, taken when lead-212 was in secular equilibrium with radium-224, were interpreted as representing the lead-212 diffusion length. The aim of this work is to provide first experimental estimates for the diffusion length of radon-220, using a new methodology. METHODS: The diffusion length of radon-220 was estimated from autoradiography measurements of histological sections taken from 24 mice-borne subcutaneous tumors of five different types. Unlike previous studies, the source dwell time inside the tumor was limited to 30 min, to prevent the buildup of lead-212. To investigate the contribution of potential non-diffusive processes, experiments were done in two sets: fourteen in vivo tumors, where during the treatment the tumors were still carried by the mice with active blood supply, and 10 ex-vivo tumors, where the tumors were excised before source insertion and kept in a medium at 37 ∘ C $37^\circ {\text{C}}$ with the source inside. RESULTS: The measured diffusion lengths of radon-220, extracted by fitting the recorded activity pattern up to 1.5 mm from the source, lie in the range 0.25 - 0.6 mm ${0.25-0.6}\nobreakspace {\text{mm}}$ , with no significant difference between the average values measured in in-vivo and ex-vivo tumors: L R n i n - v i v o = 0.40 ± 0.08 mm $L_{Rn}^{in-vivo}=0.40{\pm }0.08\nobreakspace {\text{mm}}$ versus L R n e x - v i v o = 0.39 ± 0.07 mm $L_{Rn}^{ex-vivo}=0.39{\pm }0.07\nobreakspace {\text{mm}}$ . However, in-vivo tumors display an enhanced spread of activity 2-3 mm away from the source. This effect is not explained by the current model and is much less pronounced in ex-vivo tumors. CONCLUSIONS: The average measured radon-220 diffusion lengths in both in-vivo and ex-vivo tumors are consistent with published data on the diffusion length of radon in water and lie close to the upper limit of the previously estimated range of 0.2 - 0.4 mm $0.2-0.4\nobreakspace {\text{mm}}$ . The observation that close to the source there is no apparent difference between in-vivo and ex-vivo tumors, and the good agreement with the theoretical model in this region suggest that the spread of radon-220 is predominantly diffusive in this region. The departure from the model prediction in in-vivo tumors at large radial distances may hint at potential vascular contribution, which will be the subject of future works.

Charting the Course of Targeted α Therapy With First-in-Human, Postadministration Image-Guided Dosimetry and Response Assessment of 212 Pb-VMT-α-NET in Metastatic Neuroendocrine Tumors.

ABSTRACT: 212 Pb emerges as a compelling in vivo α-particle generator for targeted α therapy due to its favorable half-life ( t1/2 = 10.6 hours) aligning with the biological half-lives of small peptides and its potent α-particle emissions within the decay series. However, one of the challenges with 212 Pb is to perform appropriate image-guided dosimetry. To date, all the data have been extrapolated from its imaging analog, 203 Pb. We present the first-in-human posttherapy image-guided dosimetric estimates of a single cycle of 212 Pb VMT-α-peptide, administered in a 41-year-old woman with an advanced grade 2 NET. The patient also demonstrated partial response on treatment.

210Po and 210Pb radioactivity levels in local and imported tobacco used in Palestine and Jordan.

This study aimed to assess the concentrations of 210Po and 210Pb in various tobacco samples from Palestine and Jordan. Cigarette smoking is recognized as a significant contributor to the radiation dose received by individuals, primarily due to the elevated levels of 210Pb and 210Po found in tobacco. The analysis revealed that the average concentrations of 210Po in locally sourced tobacco and cigarette samples in Palestine are 16.8 ± 2.3 mBq/g and 18.5 ± 2.0 mBq/g, with a total average of 17.8 ± 7.4 mBq/g (15.5 mBq/cigarette). Similarly, the average concentrations of 210Pb in these samples are 18.5 ± 2.6 mBq/g and 20.3 ± 2.2 mBq/g, with a total average of 19.6 ± 8.1 mBq/g (17.0 mBq/cigarette). In Jordan, the average concentrations of 210Po in cigarette samples and narghile tobacco are 20.1 ± 2.4 mBq/g and 18.3 ± 4.1 mBq/g, with a total average value of 19.6 ± 9.9 mBq/g (18.0 mBq/cigarette), while the average concentrations of 210Pb are 22.2 ± 2.6 mBq/g and 20.2 ± 4.5 mBq/g, with a total average value of 21.6 ± 10.8 mBq/g (19.9 mBq/cigarette). The annual effective doses resulting from inhalation were calculated for smokers of these samples. The findings revealed that the levels of 210Po and 210Pb radioactivity in certain investigated samples exceeded the results of studies in many countries of the world. The associated effective doses per year from smoking for all brands products in Palestine range from 34.7 µSv/y to 186.5 µSv/y with an average of 109.5 µSv/y, while in Jordan 54.5 µSv/y to 289.1 µSv/y with an average of 130.9 µSv/y.

A diffusion-leakage model coupled with dose point kernels (DPK) for dosimetry of diffusing alpha-emitters radiation therapy (DaRT).

BACKGROUND: Diffusing alpha-emitters radiation therapy (DaRT) is a novel brachytherapy technique that leverages the diffusive flow of 224Ra progeny within the tumor volume over the course of the treatment. Cell killing is achieved by the emitted alpha particles that have a short range in tissue and high linear energy transfer. The current proposed absorbed dose calculation method for DaRT is based on a diffusion-leakage (DL) model that neglects absorbed dose from beta particles. PURPOSE: This work aimed to couple the DL model with dose point kernels (DPKs) to account for dose from beta particles as well as to consider the non-local deposition of energy. METHODS: The DaRT seed was modeled using COMSOL multiphysics and the DL model was implemented to extract the spatial information of the diffusing daughters. Using Monte-Carlo (MC) methods, DPKs were generated for 212Pb, 212Bi, and their progenies since they were considered to be the dominant beta emitters in the 224Ra radioactive decay chain. A convolution operation was performed between the integrated number densities of the diffusing daughters and DPKs to calculate the total absorbed dose over a 30-day treatment period. Both high-diffusion and low-diffusion cases were considered. RESULTS: The calculated DPKs showed non-negligible energy deposition over several millimeters from the source location. An absorbed dose >10 Gy was deposited within a 1.8 mm radial distance for the low diffusion case and a 2.2 mm radial distance for the high diffusion case. When the DPK method was compared with the local energy deposition method that solely considered dose from alpha particles, differences above 1 Gy were found within 1.3 and 1.8 mm radial distances from the surface of the source for the low diffusion and high diffusion cases, respectively. CONCLUSIONS: The proposed method enhances the accuracy of the dose calculation method used for the DaRT technique.

Assessment of Be-7, Pb-210 and Po-210 Activities in Airborne Particulate Matter Over Istanbul, Türkiye.

Airborne particulate matter is one of the air pollutants which can have detrimental health effects in the human body. Radionuclides adsorb onto air particles and make their way to humans primarily through inhalation. Naturally-occurring radionuclides, 210Pb and 210Po, are of notable health concern due to their relatively elevated ingestion and inhalation doses. In the current study, activity concentrations of 7Be, 210Pb and 210Po were determined in air particulate matter (PM). PM2.5 was collected on the European side, while PM10 was collected on the Anatolian side of Istanbul. Be-7, 210Pb and 210Po activities were found to be 5.17 ± 2.35, 0.96 ± 0.42; 0.25 ± 0.14 mBq m- 3 in Anatolian side, respectively. Be-7, 210Pb and 210Po activities were found to be 3.81 ± 2.27, 0.62 ± 0.29, 0.29 ± 0.26, mBq m- 3 in European side, respectively. The ratio of 210Po/210Pb was found to be higher (0.47 ± 0.31 for PM2.5 and 0.34 ± 0.27 for PM10) than the global average of 0.1. This result can be explained by the fact that Po is more volatile than Pb and enhanced in the air by the combustion process. Inhalation dose rates of 210Pb and 210Po due to PM10 exposure were calculated to be 7.70 ± 3.30 and 4.05 ± 2.31 µSv year- 1, respectively. Pb-210 bioaccessibility was assessed by the extraction of the particles in simulated lung fluids. Approximately 24.8% of inhaled 210Pb was estimated to be bioaccessible. This study suggests that 210Po and 210Pb activities are partially enhanced in the air particles in Istanbul and should be regularly monitored.

Virtual calibration for in vivo measurement of Pb-210 activity in the skull using BOMAB, MIRD, and MIDA phantoms.

The counting efficiency calibration for in vivo measurement is crucial to derive the activity of radionuclides residing inside a monitored subject. Recently, virtual calibration based on computational phantoms has become popular, yet some key questions remain unresolved. Here, we focus on the in vivo measurement of Pb-210 in the skull and systematically examine how virtual calibration compares to those using physical phantoms and how the variety of computational phantoms affects the derived counting efficiency. It is found that the virtually calibrated efficiency based on the MIDA phantom, which characterizes the highest anatomical fidelity, shows reasonable consistency with the experimental counterpart, with a relative bias of approximately 10%. However, in comparison to the case based on the MIDA phantom, those based on the BOMAB and MIRD phantoms show larger deviation, demonstrating underestimations on the counting efficiency by 51% and 42%, respectively. This finding underscores the critical role of computational phantoms in the virtual calibration. This study contributes to the development of techniques for assessing lung cancer risk resulting from chronic radon exposure through in vivo measurement of skeletal Pb-210 activity.

Using VARSKIN+v1.2 to estimate dose from direct skin contamination with radionuclides 223 Ra, 212 Pb and 225 Ac; considerations for Nuclear Medicine staff and associated Personal Protective Equipment (PPE).

OBJECTIVE: To calculate depth-weighted doses for 223 Ra, 212 Pb and 225 Ac for the skin sites of trunk, arms/legs, face, wrist, back of hand, fingertip, back and side of fingers using VARSKIN+v1.2. METHODS: Published depth distribution histograms of the basal cells were used with dose averaging in VARSKIN+v1.2. A density correction factor was applied for the 1 g/cc within VARSKIN. Results were compared to the regulatory 70 µm depth and to average depth values for the skin sites. RESULTS: 223 Ra has no alpha component at the regulatory 70 µm. This dose is exceeded by the depth-weighted dose rates for all sites (except the fingertip) with factors ×74 (back of finger) to x3600 (trunk). 212 Pb and 225 Ac have alpha contributions at 70 µm. . For 212 Pb, this dose value is greater by over ×2 than the depth-weighted dose rate for the wrist, back of hand, and finger sites, and underestimates dose rates for the other sites. For 225 Ac, the 70µm dose rate is exceeded by the depth-weighted dose rates for the trunk, face, arms/legs by factors of ×4-10. Using fixed depth values, the depth-weighted dose rates are larger for all sites except the fingertip. The skin dose is also calculated for biological half-lives of 1, 3 and 6 h. Using the depth-weighted dose rates and a 3 h biological half-life, the activity for 500 mSv is in the range 9-177 Bq for the trunk, face, arms/legs, wrist and hand for all three radionuclides. CONCLUSION: For alpha-emitting radionuclides a depth-weighted calculation gives more representative dose values. The very low activity values for 500 mSv skin dose to be exceeded have implications for appropriate staff PPE and training.

Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors.

PURPOSE: The lead-203 (203Pb)/lead-212 (212Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for cancer. Emerging evidence suggests that 212Pb-labeled peptide-based radiopharmaceuticals targeting somatostatin receptor subtype 2 (SSTR2) may provide improved effectiveness compared to beta-particle-based therapies for neuroendocrine tumors (NETs). This study aims to improve the performance of SSTR2-targeted radionuclide imaging and therapy through structural modifications to Tyr3-octreotide (TOC)-based radiopharmaceuticals. METHODS: New SSTR2-targeted peptides were designed and synthesized with the goal of optimizing the incorporation of Pb isotopes through the use of a modified cyclization technique; the introduction of a Pb-specific chelator (PSC); and the insertion of polyethylene glycol (PEG) linkers. The binding affinity of the peptides and the cellular uptake of 203Pb-labeled peptides were evaluated using pancreatic AR42J (SSTR2+) tumor cells and the biodistribution and imaging of the 203Pb-labeled peptides were assessed in an AR42J tumor xenograft mouse model. A lead peptide was identified (i.e., PSC-PEG2-TOC), which was then further evaluated for efficacy in 212Pb therapy studies. RESULTS: The lead radiopeptide drug conjugate (RPDC) - [203Pb]Pb-PSC-PEG2-TOC - significantly improved the tumor-targeting properties, including receptor binding and tumor accumulation and retention as compared to [203Pb]Pb-DOTA0-Tyr3-octreotide (DOTATOC). Additionally, the modified RPDC exhibited faster renal clearance than the DOTATOC counterpart. These advantageous characteristics of [212Pb]Pb-PSC-PEG2-TOC resulted in a dose-dependent therapeutic effect with minimal signs of toxicity in the AR42J xenograft model. Fractionated administrations of 3.7 MBq [212Pb]Pb-PSC-PEG2-TOC over three doses further improved anti-tumor effectiveness, resulting in 80% survival (70% complete response) over 120 days in the mouse model. CONCLUSION: Structural modifications to chelator and linker compositions improved tumor targeting and pharmacokinetics (PK) of 203/212Pb peptide-based radiopharmaceuticals for NET theranostics. These findings suggest that PSC-PEG2-TOC is a promising candidate for Pb-based targeted radionuclide therapy for NETs and other types of cancers that express SSTR2.