RESUMO
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.
Assuntos
Bivalves , Monitoramento de Radiação , Poluentes Radioativos da Água , Animais , Índia , Poluentes Radioativos da Água/análise , Polônio/análise , Tório/análise , Radioisótopos de Chumbo/análise , HumanosRESUMO
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 0.12â¯mBqâ¯g-1 dry weight in the fruits of the common chestnut (Aesculus hippocastanum) to 19.7â¯mBqâ¯g-1 dw in herb of ground elder (Aegopodium podagraria) for 210Po, while for 210Pb ranged from 0.16â¯mBqâ¯g-1 dw to 34.3â¯mBqâ¯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⯵Sv from 210Po and 0.02-98.2⯵Sv 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.
Assuntos
Radioisótopos de Chumbo , Plantas Medicinais , Polônio , Polônio/análise , Radioisótopos de Chumbo/análise , Plantas Medicinais/química , Humanos , Medição de Risco , NeoplasiasRESUMO
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.
Assuntos
Partículas alfa , Tumores Neuroendócrinos , Humanos , Feminino , Adulto , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Partículas alfa/uso terapêutico , Radiometria , Metástase Neoplásica , Radioisótopos de Chumbo , Radioterapia Guiada por Imagem , Resultado do TratamentoRESUMO
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.
Assuntos
Partículas alfa , Radônio , Animais , Camundongos , Partículas alfa/uso terapêutico , Difusão , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias/radioterapia , Rádio (Elemento)/uso terapêutico , Radioisótopos de ChumboRESUMO
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.
Assuntos
Radioisótopos de Chumbo , Plantas Medicinais , Polônio , Radioisótopos de Chumbo/análise , Ucrânia , Plantas Medicinais/química , Polônio/análise , Neoplasias , Monitoramento de Radiação/métodos , Medição de Risco , HumanosRESUMO
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.
Assuntos
Polônio , Radioatividade , Produtos do Tabaco , Jordânia , Chumbo/análise , Radioisótopos de Chumbo/análise , Polônio/análise , Produtos do Tabaco/análiseRESUMO
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.
Assuntos
Chumbo , Contagem Corporal Total , Contagem Corporal Total/métodos , Simulação por Computador , Calibragem , Método de Monte Carlo , Radioisótopos de Chumbo , Crânio , Imagens de FantasmasRESUMO
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.
Assuntos
Partículas alfa , Método de Monte Carlo , Radiometria , Dosagem Radioterapêutica , Partículas alfa/uso terapêutico , Difusão , Braquiterapia/métodos , Radioisótopos de Chumbo/uso terapêutico , Bismuto/uso terapêutico , Humanos , Partículas beta/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
The radon decay product 210Pb is a known component of tobacco. In this study, the activity concentration of 210Pb in the most popular cigarette brands (six samples) for Kazakhstan consumers was determined by beta spectrometry. The activity levels of 210Pb ranged between 2.69 ± 0.27 and 27.42 ± 2.74 mBq per cigarette. Higher activity concentrations for 210Pb were found in Sample No.4 and showed an excess of the world average by 1.8 times. The average activity concentrations of 210Pb in cigarette tobacco were 10.42 ± 1.04 mBq cig-1. The daily activities inhaled in the lungs of a smoker, and the resulting effective doses due to cigarette smoking were calculated. Effective doses per year due to cigarette smoking were calculated assuming that 42.13% of the 210Pb in tobacco were retained in the lungs of the smokers. It is concluded that for a smoker in Kazakhstan, the average effective dose ranges from 9.1 ± 0.9 µSv/year to 92.8 ± 9.3 µSv/year for a cigarette consumption of one pack of cigarettes per day. The results indicate that the annual effective doses from inhalation of 210Pb due to smoking one pack of cigarettes per day are from 7 to 58 times (for different types of cigarettes) greater than the annual effective doses from ingestion of radionuclides via the diet.
Assuntos
Polônio , Produtos do Tabaco , Cazaquistão , Chumbo , Radioisótopos de Chumbo/análise , Polônio/análiseRESUMO
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.
Assuntos
Tumores Neuroendócrinos , Octreotida , Camundongos , Humanos , Animais , Octreotida/uso terapêutico , Octreotida/metabolismo , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/tratamento farmacológico , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Chumbo , Radioisótopos de Chumbo , Receptores de Somatostatina/metabolismo , QuelantesRESUMO
Molecular changes in malignant tissue can lead to an increase in the expression levels of various proteins or receptors that can be used to target the disease. In oncology, diagnostic imaging and radiotherapy of tumors is possible by attaching an appropriate radionuclide to molecules that selectively bind to these target proteins. The term "theranostics" describes the use of a diagnostic tool to predict the efficacy of a therapeutic option. Molecules radiolabeled with γ-emitting or ß+-emitting radionuclides can be used for diagnostic imaging using single photon emission computed tomography or positron emission tomography. Radionuclide therapy of disease sites is possible with either α-, ß-, or Auger-emitting radionuclides that induce irreversible damage to DNA. This Focus Review centers on the chemistry of theranostic approaches using metal radionuclides for imaging and therapy. The use of tracers that contain ß+-emitting gallium-68 and ß-emitting lutetium-177 will be discussed in the context of agents in clinical use for the diagnostic imaging and therapy of neuroendocrine tumors and prostate cancer. A particular emphasis is then placed on the chemistry involved in the development of theranostic approaches that use copper-64 for imaging and copper-67 for therapy with functionalized sarcophagine cage amine ligands. Targeted therapy with radionuclides that emit α particles has potential to be of particular use in late-stage disease where there are limited options, and the role of actinium-225 and lead-212 in this area is also discussed. Finally, we highlight the challenges that impede further adoption of radiotheranostic concepts while highlighting exciting opportunities and prospects.
Assuntos
Radioisótopos de Cobre , Medicina Nuclear , Masculino , Humanos , Radioisótopos de Chumbo , Lutécio/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Radioimunoterapia , Masculino , Animais , Humanos , Radioimunoterapia/métodos , Chumbo , Partículas alfa , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Radioisótopos de Chumbo/uso terapêutico , Proteína Cofatora de MembranaRESUMO
Algae are believed to give health benefits. However, the studies showed they contain toxic elements, including radionuclides, and may affect human health. The study presents the values of activity concentrations of 210Po and 210Pb in the algae supplements available worldwide for adults. The activity concentrations (Bq/kg dw) ranged from 0.07 to 14.5 (210Po) and from 0.06 to 8.48 (210Pb). Also, the effective radiation doses and the cancer risk from 210Po and 210Pb decay ingested with analyzed algal supplements have been assessed. The highest values of annual effective doses have been estimated for 210Po in the recommended portion of Spirulina (Arthrospira platensis) from China (59.7 µSv/year) and Diatomaceous earth from the USA (50.4 µSv/year). The cancer morbidity and mortality risk ranged from 10-4 to 10-8. The study indicated the activity concentrations of 210Po and 210Pb were low, and algae supplements for human consumption could be considered safe food.
Assuntos
Polônio , Monitoramento de Radiação , Humanos , Chumbo , Radioisótopos de Chumbo/análise , Polônio/análise , DietaRESUMO
The concentrations of polonium 210Po and radio-lead 210Pb in cannabis (Cannabis sativa L.) plants and products now legally available in Poland were determined. Limiting the delivery of radionuclides to the body is an important aspect of civil protection in many countries. Reduction in use and awareness of the risks associated with tobacco and cannabis smoking have a great impact. The 210Po and 210Pb concentrations in 44 hemps, 20 hashish and 8 hemp tea samples, as well as in 3 types of cannabis plants (highest parts of mature hemp plant Fenola, Fedora and Futura) were determined. Each of the sample names means a different type and cross of C. sativa L. Being numerous, the are recognized on the market precisely by these names. Effective doses were calculated and compared to the doses of the other combustion products, such as tobacco. In the case of hemp, the highest concentration of 210Po was found in samples of dried Sweet Carmel (34.7 ± 0.23 mBq·g-1), while the lowest in the Hemp Berry (0.57 ± 0.23 mBq·g-1). In the case of 210Pb, the highest concentration was in Strawberry Kush (2.32 ± 0.05 mBq·g-1), while the lowest in Strawberry Haze (0.19 ± 0.03 mBq·g-1). In hashish, the highest and lowest concentrations of 210Po were in Strawberry Diesel 164 ± 3 mBq·g-1 and in Mango Kush 2.5 ± 0.2 mBq·g-1. The highest and lowest concentrations in the case of 210Pb in hashish were in Pollen Hashish 45.1 ± 0.2 mBq·g-1 and in Mango Kush Hashish 0.45 ± 0.05 mBq·g-1, respectively. These radionuclides did not constitute a radioactive equilibrium (210Po/210Pb).
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Cannabis , Polônio , Monitoramento de Radiação , Chumbo , Radioisótopos de Chumbo/análise , Polônio/análise , Monitoramento de Radiação/métodosRESUMO
This article contains and discusses the results of research on the source of polonium 210Po and radio-lead 210Pb in the human body of adults living in Poland. An adult inhabitant of Poland receives an effective annual radiation dose of 309 µSv from inhalation and absorption of 210Po and 210Pb. The main sources of both radionuclides in the body is cigarette and marijuana smoking. In terms of food, the consumption of fish, cereals, vegetables and fruit as well as mushrooms have the largest contribution to annual dose. This study highlights the importance of cigarette smoking and the growing importance of marijuana hash smoking as the main source of 210Po and 210Pb for adults living in Poland. The calculated dose that results from the decay of both radionuclides in body is 1/10 of the annual radiation dose received by a Polish inhabitant from natural sources (2.8 mSv) and is almost five times lower than the dose resulting from the inhalation of 222Rn.
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Polônio , Monitoramento de Radiação , Animais , Corpo Humano , Humanos , Chumbo , Radioisótopos de Chumbo/análise , Polônia , Polônio/análise , Monitoramento de Radiação/métodosRESUMO
Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the ß-particle emitter 177Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of 177Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as 212Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating 212Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of 177Lu/90Y/111In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with 212Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, 212Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.
Assuntos
Tumores Neuroendócrinos , Compostos Organometálicos , Quelantes/efeitos adversos , Humanos , Chumbo , Radioisótopos de Chumbo , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/radioterapia , Octreotida/efeitos adversos , Compostos Organometálicos/efeitos adversos , Tomografia por Emissão de Pósitrons , Cintilografia , Compostos Radiofarmacêuticos/efeitos adversos , Receptores de Somatostatina , Somatostatina/efeitos adversosRESUMO
This study provides the first data set of 210Po and 210Pb activity concentrations in the organic and inorganic components of several particle size classes of aerosols collected at two sampling stations in Kuwait. The 210Po concentrations in the aerosols (Bq/g) were similar in all of the particle size classes, but as most (91%) of the aerosol load was made of fine fraction particles of PM0.39-2.5 µm, most of the 210Po activity was carried by this aerosol fraction. At the two sampling stations, the 210Po/210Pb activity concentration ratios in the aerosols were similar, stable around the year, and averaged 1.5 (range 1.2-1.9), much higher than the typical activity concentration ratios of these radionuclides in unmodified (background) aerosols, with Po/Pb < 0.1. The aerosol enrichment in 210Po was likely originated from the oil industry, specifically by gas flaring and oil refining in the Gulf region. Radionuclide analysis in the organic and inorganic components of aerosols showed that the 210Po concentration in the organic component was one order of magnitude higher than the 210Po concentration in the inorganic component, in contrast with 210Pb, which displayed similar concentrations in both organic and inorganic aerosol components. The 210Po carrying organic component of aerosols was investigated and it was found to be largely composed of microorganisms with high microbial and fungi diversity, with the phyla Proteobacteria, Ascomycota, and Basidiomycota being dominant among the bacteria and with Zygomycota being dominant among the fungi. Therefore, we are facing an active concentration process of the atmospheric 210Po carried out by microorganisms, which underlies the 210Po enrichment process in the organic component of aerosols. This bioconcentration of polonium in bioaerosols was unknown.
Assuntos
Poluentes Radioativos do Ar , Polônio , Monitoramento de Radiação , Aerossóis/análise , Poluentes Radioativos do Ar/análise , Radioisótopos de Chumbo/análise , Polônio/análiseRESUMO
Two radiopharmaceutical preparations were developed on the basis of artificial targeted polypeptide ZHER2 specific to HER2/neu tumor marker and radionuclides 177Lu (ZHER2-HSA-chelator-177Lu) or 212Pb (ZHER2-HSA-chelator-212Pb). The objective was to evaluate in vitro the cytotoxic activity of the targeted radiopharmaceuticals using two cultured human breast cancer cell lines with different expression of HER2/neu: SK-BR3 (high expression of HER2/neu) and MCF-7 (low expression of HER2/neu). It was shown that the cytotoxic effect of both preparations was significantly higher against the SK-BR-3 cells. The cytotoxicity correlated with the incubation period (it was higher after 72 h than after 24 h) and was significantly more pronounced in comparison with activity of radionuclide salts without a specific ligand. In vivo preclinical study of these pharmaceuticals seems to be very promising in animals with xenografted tumors showing high expression of HER2/neu marker.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/radioterapia , Imunotoxinas/uso terapêutico , Radioisótopos de Chumbo/uso terapêutico , Lutécio/uso terapêutico , Radioisótopos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Radioisótopos de Chumbo/química , Células MCF-7 , Terapia de Alvo Molecular/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Especificidade por SubstratoRESUMO
In this study, the activity concentrations levels of 210Pb and 210Po in the edible portions of eight seafood samples collected from the Fujian coast of China were determined. The activity concentrations ranged from 0.74 ± 0.08 to 12.6 ± 1.0 Bq/kg for 210Po and from the minimum detectable limit (MDL, 0.80 Bq/kg) to 11. 7 ± 1.1 Bq/kg for 210Pb. The 210Po activity concentration in all the fish organs ranged from 0.68 to 204 Bq/kg (w.w.), and the 210Po activity was mainly concentrated in the stomach, spleen, heart, liver, gonad, and intestine samples. The 210Pb activity concentration in all the fish organs ranged from the MDL to 15.2 Bq/kg (w.w.), and the 210Pb activity was concentrated in the head, fish scale, and gill samples. The annual effective ingestion doses ranged from 82.8 to 255 µSv/a for all age groups, and the lifetime risk of cancers were estimated. Both the effective ingestion doses and cancer risk to humans were within the acceptable ranges.
Assuntos
Polônio , Monitoramento de Radiação , Poluentes Radioativos da Água , Animais , China , Humanos , Chumbo , Radioisótopos de Chumbo/análise , Polônio/análise , Alimentos Marinhos/análise , Poluentes Radioativos da Água/análiseRESUMO
The activity concentrations of 210Pb and 210Po in the most popular cigarettes and moassel tobacco brands consumed in Egypt were determined by the spontaneous deposition method using alpha spectrometry. It turned out that the activity concentration of 210Po was higher than that of 210Pb in all tobacco brands. Higher activity concentrations for both 210Pb and 210Po were found in cigarette than in moassel tobacco. The average activity concentrations of 210Pb and 210Po in cigarette tobacco were 11.79 ± 1.67 and 15.00 ± 1.83 mBq cig-1, respectively, whereas in moassel tobacco the values were 7.08 ± 1.91 and 9.12 ± 1.12 mBq g-1, respectively. The daily activities inhaled in the lung of a smoker and the inhalation effective doses due to cigarette and shisha smoking were calculated. The results revealed that the total 210Pb and 210Po daily activities inhaled and the total annual inhalation effective doses due to shisha smoking were two times greater than the corresponding values due to cigarette smoking. Also, the results indicated that the annual effective doses from inhalation of 210Pb and 210Po due to smoking 20 cigarettes per day are 14 and 16 times greater than the annual ingestion doses from the diet, respectively. In contrast, the annual effective doses from inhalation of 210Pb and 210Po due to shisha smoking (27 g moassel tobacco per day) are 26 and 33 times greater than the annual ingestion doses from the diet, respectively.