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1.
Theranostics ; 11(20): 9721-9737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815780

RESUMO

Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223Ra, 225Ac and 227Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223Ra, 225Ac, and 227Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223Ra, 225Ac, and 227Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Actínio/farmacocinética , Partículas alfa/uso terapêutico , Animais , Disponibilidade Biológica , Calibragem , Humanos , Imagens de Fantasmas , Radioisótopos , Rádio (Elemento)/farmacocinética , Tório/farmacocinética , Tomografia Computadorizada por Raios X/métodos
2.
Cancer Biother Radiopharm ; 35(7): 540-548, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32486837

RESUMO

Thorium-227 (227Th) is a long-lived (T1/2 = 18.7 d) α-emitter that has emerged as candidate for radioimmunotherapy. Imaging of patients treated with thorium-227 conjugates is challenging due to the low activity administered and to photon emissions with low yields. In addition, the radioactive daughter radium-223 (223Ra) have photon emissions in the same energy range as 227Th. The long half-life of 223Ra (T1/2 = 11.4 d) and the possibility of redistribution motivates efforts to separate 227Th and 223Ra. The aim of this study was to investigate the feasibility of imaging of patients treated with 227Th-labeled-monoclonal antibody (mAb) and to determine acquisition and image processing parameters to enable discrimination between 227Th and 223Ra. Imaging was performed with a GE Discovery 670 NM/CT γ-camera. Radionuclide separation with different energy windows (EW) and collimators was studied in images of vials with either 227Th or 223Ra. Phantom acquisitions with clinically relevant activities were performed to assess image quality and the usefulness of background subtraction and spatial filtering. Two patients treated with 227Th-labeled-mAb were imaged. Imaging of vials showed that 223Ra can be distinguished from 227Th using multiple energy windows. Medium- and high-energy collimators showed similar performance of sensitivity and spatial resolution, whereas the low-energy collimator had higher sensitivity but poor resolution due to collimator penetration. Visually, the image quality was improved with background subtraction and spatial filtering. The patient images exhibited the expected image quality and a possibility to separate 227Th and 223Ra. γ-Camera imaging of patients treated with 227Th-mAb is feasible and 223Ra can be distinguished from 227Th. Image quality is substantially improved using background subtraction and a spatial smoothing filter. Acquisition settings recommended for planar images are: high-energy general purpose or medium-energy general purpose collimator, 40 min acquisition time and energy windows: (1) 70-100 keV (227Th and 223Ra); (2) 215-260 keV (227Th); (3) 260-290 keV (223Ra); (4) 350-420 keV (223Ra).


Assuntos
Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/farmacocinética , Rádio (Elemento)/farmacocinética , Tório/farmacocinética , Ensaios Clínicos Fase I como Assunto , Estudos de Viabilidade , Câmaras gama , Meia-Vida , Humanos , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Radiometria/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Rádio (Elemento)/administração & dosagem , Espectrometria gama/instrumentação , Espectrometria gama/métodos , Tório/administração & dosagem , Distribuição Tecidual
3.
Cancer Biother Radiopharm ; 35(7): 530-539, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32429699

RESUMO

Introduction: Thorium-227 is an alpha-emitting radioisotope with potential therapeutic applications in targeted alpha therapy. Thorium-227 decays to Radium-223, which may have an independent biodistribution to that of the parent Thorium-227 radiopharmaceutical. Quantitative in vivo imaging with sodium iodide (NaI) detectors is challenging due to cross-talk between neighboring γ-photopeaks as well as scattered γ-photons. The aim of this work was to validate the use of a spectral analysis technique to estimate the activity of each isotope within a region of interest applied to a pair of conjugate view planar acquisitions, acquired at multiple energy windows. Methods: Energy spectra per unit activity arising from unscattered Thorium-227 photons and Radium-223 photons as well as from scattered photons were modeled. These spectra were scaled until the combination of these component spectra resulted in the closest match to the measured data in four energy windows. Results: Measured estimates of activity followed the known decay curves in phantoms representative of a human torso. The mean errors in estimating Thorium-227 and Radium-223 were 5.1% (range -8.0% to 40.0%) and 3.4% (range -50.0% to 48.7%), respectively. The differences between the integrals of the theoretical and estimated time activity curve were <10% for both Thorium-227 and Radium-223. Conclusion: γ-camera quantification of Thorium-227 and Radium-223 can be achieved by using multiple energy window acquisitions.


Assuntos
Modelos Teóricos , Compostos Radiofarmacêuticos/farmacocinética , Rádio (Elemento)/farmacocinética , Tório/farmacocinética , Câmaras gama , Humanos , Modelos Anatômicos , Imagens de Fantasmas , Radiometria/métodos , Espectrometria gama/instrumentação , Espectrometria gama/métodos , Distribuição Tecidual , Tronco/diagnóstico por imagem
4.
Naunyn Schmiedebergs Arch Pharmacol ; 393(2): 167-176, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31482261

RESUMO

Assessment of the hazardous effects of thorium, a naturally radioactive element, on the nervous and endocrine systems, which are intimately involved in maintaining homeostasis, is important. In the present study, rats were divided into control and thorium groups and were decapitated after 2, 4, and 6 weeks. We observed that intraperitoneally injected thorium (6.3 mg/kg body weight) crossed the blood-brain barrier and was localized in the cerebellum, cerebral cortex, and hypothalamus of the rats in the given order. Thorium administration significantly decreased the GSH level and increased MDA, NO, and Fe3+ levels. Furthermore, thorium administration decreased NE and DA levels and induced fluctuations in 5-HT level. Thorium administration also increased serum TSH level, which in turn increased T4 and T3 levels. Together, these results indicate that thorium administration stimulates TSH secretion, which significantly increases T4 and T3 secretion from the thyroid gland. Moreover, these results indicate that thorium administration exerts hazardous effects on the neuroendocrine axis.


Assuntos
Encéfalo/efeitos dos fármacos , Neurotransmissores/metabolismo , Tório/toxicidade , Hormônios Tireóideos/sangue , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Ratos , Serotonina/metabolismo , Tório/farmacocinética
5.
Int J Radiat Oncol Biol Phys ; 105(2): 410-422, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31255687

RESUMO

PURPOSE: Fibroblast growth factor receptor 2 (FGFR2) has been previously reported to be overexpressed in several types of cancer, whereas the expression in normal tissue is considered to be moderate to low. Thus, FGFR2 is regarded as an attractive tumor antigen for targeted alpha therapy. This study reports the evaluation of an FGFR2-targeted thorium-227 conjugate (FGFR2-TTC, BAY 2304058) comprising an anti-FGFR2 antibody, a chelator moiety covalently conjugated to the antibody, and the alpha particle-emitting radionuclide thorium-227. FGFR2-TTC was assessed as a monotherapy and in combination with the DNA damage response inhibitor ATRi BAY 1895344. METHODS AND MATERIALS: The in vitro cytotoxicity and mechanism of action were evaluated by determining cell viability, the DNA damage response marker γH2A.X, and cell cycle analyses. The in vivo efficacy was determined using human tumor xenograft models in nude mice. RESULTS: In vitro mechanistic assays demonstrated upregulation of γH2A.X and induction of cell cycle arrest in several FGFR2-expressing cancer cell lines after treatment with FGFR2-TTC. In vivo, FGFR2-TTC significantly inhibited tumor growth at a dose of 500 kBq/kg in the xenograft models NCI-H716, SNU-16, and MFM-223. By combining FGFR2-TTC with the ATR inhibitor BAY 1895344, an increased potency was observed in vitro, as were elevated levels of γH2A.X and inhibition of FGFR2-TTC-mediated cell cycle arrest. In the MFM-223 tumor xenograft model, combination of the ATRi BAY 1895344 with FGFR2-TTC resulted in significant tumor growth inhibition at doses at which the single agents had no effect. CONCLUSIONS: The data provide a mechanism-based rationale for combining the FGFR2-TTC with the ATRi BAY 1895344 as a new therapeutic approach for treatment of FGFR2-positive tumors from different cancer indications.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Neoplasias da Mama/radioterapia , Inibidores de Proteínas Quinases/uso terapêutico , Radioimunoterapia/métodos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/uso terapêutico , Tório/uso terapêutico , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes/uso terapêutico , Dano ao DNA , Combinação de Medicamentos , Sinergismo Farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Histonas/metabolismo , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Camundongos , Camundongos Nus , Terapia de Alvo Molecular/métodos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Tório/farmacocinética , Compostos de Tório/uso terapêutico , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Clin Cancer Res ; 25(15): 4723-4734, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31064781

RESUMO

PURPOSE: Targeted thorium-227 conjugates (TTC) represent a new class of molecules for targeted alpha therapy (TAT). Covalent attachment of a 3,2-HOPO chelator to an antibody enables specific complexation and delivery of the alpha particle emitter thorium-227 to tumor cells. Because of the high energy and short penetration range, TAT efficiently induces double-strand DNA breaks (DSB) preferentially in the tumor cell with limited damage to the surrounding tissue. We present herein the preclinical evaluation of a mesothelin (MSLN)-targeted thorium-227 conjugate, BAY 2287411. MSLN is a GPI-anchored membrane glycoprotein overexpressed in mesothelioma, ovarian, pancreatic, lung, and breast cancers with limited expression in healthy tissue. EXPERIMENTAL DESIGN: The binding activity and radiostability of BAY 2287411 were confirmed bioanalytically. The mode-of-action and antitumor potency of BAY 2287411 were investigated in vitro and in vivo in cell line and patient-derived xenograft models of breast, colorectal, lung, ovarian, and pancreatic cancer. RESULTS: BAY 2287411 induced DSBs, apoptotic markers, and oxidative stress, leading to reduced cellular viability. Furthermore, upregulation of immunogenic cell death markers was observed. BAY 2287411 was well-tolerated and demonstrated significant antitumor efficacy when administered via single or multiple dosing regimens in vivo. In addition, significant survival benefit was observed in a disseminated lung cancer model. Biodistribution studies showed specific uptake and retention of BAY 2287411 in tumors and enabled the development of a mechanistic pharmacokinetic/pharmacodynamic model to describe the preclinical data. CONCLUSIONS: These promising preclinical results supported the transition of BAY 2287411 into a clinical phase I program in mesothelioma and ovarian cancer patients (NCT03507452).


Assuntos
Partículas alfa/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/farmacologia , Neoplasias/tratamento farmacológico , Compostos Radiofarmacêuticos/farmacologia , Tório/farmacologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/farmacocinética , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mesotelina , Mesotelioma/tratamento farmacológico , Mesotelioma/metabolismo , Mesotelioma/patologia , Mesotelioma Maligno , Camundongos , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Compostos Radiofarmacêuticos/farmacocinética , Tório/administração & dosagem , Tório/química , Tório/farmacocinética , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Bull Environ Contam Toxicol ; 97(6): 832-837, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27663445

RESUMO

This study focused on the ability of Lemna minor and Lemna gibba to remove U and Th in the tailing water of Keban, Turkey. These plants were placed in tailing water and individually fed to the reactors designed for these plants. Water and plant samples were collected daily from the mining area. The plants were ashed at 300°C for 1 day and analyzed by ICP-MS for U and Th. U was accumulated as a function of time by these plants, and performances between 110 % and 483 % for L. gibba, and between 218 % and 1194 % for L. minor, were shown. The highest Th accumulations in L. minor and L. gibba were observed at 300 % and 600 % performances, respectively, on the second day of the experiment. This study indicated that both L. gibba and L. minor demonstrated a high ability to remove U and Th from tailing water polluted by trace elements.


Assuntos
Alismatales/metabolismo , Biodegradação Ambiental , Tório/farmacocinética , Urânio/farmacocinética , Poluentes Químicos da Água/metabolismo , Mineração , Turquia
8.
Bioorg Med Chem Lett ; 26(17): 4318-21, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27476138

RESUMO

We present the synthesis and characterization of a highly efficient thorium chelator, derived from the octadentate hydroxypyridinone class of compounds. The chelator forms extremely stable complexes with fast formation rates in the presence of Th-227 (ambient temperature, 20min). In addition, mouse biodistribution data are provided which indicate rapid hepatobiliary excretion route of the chelator which, together with low bone uptake, supports the stability of the complex in vivo. The carboxylic acid group may be readily activated for conjugation through the ɛ-amino groups of lysine residues in biomolecules such as antibodies. This chelator is a critical component of a new class of Targeted Thorium Conjugates (TTCs) currently under development in the field of oncology.


Assuntos
Quelantes/química , Tório/química , Animais , Benzofuranos , Quelantes/síntese química , Quelantes/farmacocinética , Quelantes/farmacologia , Feminino , Coração/efeitos dos fármacos , Isótopos , Pulmão/efeitos dos fármacos , Camundongos , Estrutura Molecular , Quinolinas , Tório/farmacocinética , Tório/farmacologia
9.
J Environ Radioact ; 157: 60-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27010411

RESUMO

Brassica juncea var. foliosa (B. juncea var. foliosa) is a promising species for thorium (Th) phytoextraction due to its large biomass, fast growth rate and high tolerance toward Th. To further understand the mechanisms of Th tolerance, the present study investigated the subcellular distribution and chemical forms of Th found in B. juncea var. foliosa Our results indicated that in both roots and leaves, Th contents in different parts of the cells follow the order of cell wall > membranes and soluble fraction > organelles. In particular, Transmission Electron Microscope (TEM) analysis showed that Th was abundantly located in cell walls of the roots. Additionally, when plants were exposed to different concentrations of Th, we have found that Th existed in B. juncea var. foliosa with different chemical forms. Much of the Th extracted by 2% acetic acid (HAc), 1 M NaCl and HCl in roots with the percentage distribution varied from 47.2% to 62.5%, while in leaves, most of the Th was in the form of residue and the subdominant amount of Th was extracted by HCl, followed by 2% HAc. This suggested that Th compartmentation in cytosol and integration with phosphate or proteins in cell wall might be responsible for the tolerance of B. juncea var. foliosa to the stress of Th.


Assuntos
Mostardeira/metabolismo , Tório/farmacocinética , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Citosol/metabolismo , Citosol/ultraestrutura , Microscopia Eletrônica de Transmissão , Mostardeira/efeitos dos fármacos , Mostardeira/ultraestrutura , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Folhas de Planta/ultraestrutura , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/ultraestrutura , Caules de Planta/efeitos dos fármacos , Caules de Planta/metabolismo , Tório/toxicidade
10.
Radiat Prot Dosimetry ; 167(1-3): 243-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25944955

RESUMO

The naturally occurring radionuclides of (235)U, (238)U and (232)Th and their daughter products are a potential major source of anthropogenic radiation to tobacco smokers. Often overlooked is the presence of (40)K in tobacco and its implication to radiation dose accumulation in the human body. In this study, these three radiation sources have been determined in four typical US cigarettes using neutron activation analysis (NAA). The NAA reactions of (238)U(n,γ)(239)U, (232)Th(n,γ)(233)Th and (41)K(n,γ)(42)K were used to determine (235)U, (238)U and (232)Th and (40)K, respectively. The activity of (238)U can easily be determined by epithermal NAA of the (238)U(n,γ)(239)U reaction, and the activity of (235, 234)U can easily be deduced. Using isotopic ratios, the activity due to (40)K was found by the determined concentrations of (41)K (also by epithermal neutrons) in the bulk material. Each gram of total potassium yields 30 Bq of (40)K. The annual effective dose for smokers using 20 cigarettes per day was calculate to be 14.6, 137 and 9 µSv y(-1) for (238,235,) (234)U, (232)Th and (40)K, respectively. These values are significantly lower that the dose received from (210)Po except for (232)Th.


Assuntos
/química , Radioisótopos de Potássio/análise , Exposição à Radiação/análise , Fumar/metabolismo , Tório/análise , Urânio/análise , Absorção de Radiação/fisiologia , Adulto , Feminino , Humanos , Masculino , Radioisótopos de Potássio/farmacocinética , Radiometria/métodos , Medição de Risco/métodos , Tório/farmacocinética , Urânio/farmacocinética
11.
Radiat Prot Dosimetry ; 153(3): 328-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22802517

RESUMO

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.


Assuntos
Contaminação Radioativa de Alimentos , Radioisótopos/análise , Radioisótopos/farmacologia , Poluentes Radioativos da Água/análise , Adulto , Radiação de Fundo , Radioisótopos de Césio/farmacocinética , Água Potável , Exposição Ambiental , Humanos , Índia , Oryza/efeitos da radiação , Radioisótopos de Potássio/farmacocinética , Rádio (Elemento)/farmacocinética , Espectrometria gama/métodos , Tório/farmacocinética , Triticum/efeitos da radiação , Urânio/farmacocinética
12.
Radiat Prot Dosimetry ; 148(1): 121-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21325369

RESUMO

The lung counting system at Kalpakkam, India, used for the estimation of transuranics deposited in the lungs of occupational workers, consists of an array of three large area germanium detectors fixed in a single assembly. The efficiency calibration for low energy photons was carried out using ²4¹Am and ²³²Th lung sets of Lawrence Livermore National Laboratory phantom. The muscle equivalent chest wall thickness (MEQ-CWT) was derived for the three energies 59.5, 75.95 (average energy of ²³²Th) and 238.9 keV for the series of overlay plates made of different adipose mass ratios. Efficiency as a function of MEQ-CWT was calculated for individual detectors for the three energies. Variation of MEQ-CWT from 16 to 40 mm resulted in an efficiency variation of around 40 % for all the three energies. The array efficiency for different MEQ-CWT ranged from 1.4×10⁻³ to 3.2×10⁻³, 1.5×10⁻³ to 3.3×10⁻³ and 1.1×10⁻³ to 2.3×10⁻³ for 59.5, 75.95 and 238.9 keV, respectively. In the energy response, efficiency was observed to be maximum for 75.95 keV compared with 59.5 and 238.9 keV.


Assuntos
Amerício/análise , Amerício/farmacocinética , Pulmão/fisiologia , Exposição Ocupacional/análise , Radiometria/instrumentação , Tório/análise , Tório/farmacocinética , Materiais Biomiméticos , Desenho de Equipamento , Análise de Falha de Equipamento , Germânio/efeitos da radiação , Humanos , Índia , Doses de Radiação , Semicondutores
13.
Sci Total Environ ; 414: 167-76, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22115612

RESUMO

Transfer of radionuclides ((232)Th and (238)U) and associated metals (As, Cd, Pb and Cr) from soil to free-living earthworm species was investigated in a thorium ((232)Th) rich area in Norway. Sampling took place within former mining sites representing the technologically enhanced naturally occurring radioactive materials (TENORM), at undisturbed site with unique bedrock geology representing the naturally occurring radioactive materials (NORM) and at site outside the (232)Th rich area taken as reference Background site. Soil analysis revealed the elevated levels of investigated elements at NORM and TENORM sites. Based on sequential extraction, uranium ((238)U) and cadmium (Cd) were quite mobile, while the other elements were strongly associated with mineral components of soil. Four investigated earthworm species (Aporrectodea caliginosa, Aporrectodea rosea, Dendrodrilus rubidus and Lumbricus rubellus) showed large individual variability in the accumulation of radionuclides and metals. Differences in uptake by epigeic and endogeic species, as well as differences within same species from the NORM, TENORM and Background sites were also seen. Based on total concentrations in soil, the transfer factors (TF) were in ranges 0.03-0.08 and 0.09-0.25, for (232)Th and (238)U, respectively. TFs for lead (Pb), chromium (Cr) and arsenic (As) were low (less than 0.5), while TFs for Cd were higher (about 10). Using the ERICA tool, the estimated radiation exposure dose rate of the earthworms ranged from 2.2 to 3.9 µGy/h. The radiological risk for investigated earthworms was low (0.28). The obtained results demonstrated that free-living earthworm species can survive in soil containing elevated (232)Th and (238)U, as well As, Cd, Pb and Cr levels, although certain amount of radionuclides was accumulated within their bodies. The present investigation contributes to general better understanding of complex soil-to-biota transfer processes of radionuclides and metals and to assessment of risk for non-human species in the ecosystem with multiple contaminants.


Assuntos
Metais Pesados/farmacocinética , Oligoquetos/metabolismo , Solo/química , Tório/farmacocinética , Urânio/farmacocinética , Análise de Variância , Animais , Metais Pesados/análise , Noruega , Radiometria , Análise de Regressão , Especificidade da Espécie , Tório/análise , Urânio/análise
14.
Health Phys ; 100(5): 508-14, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21451321

RESUMO

The NCRP Wound Model, which describes the retention of selected radionuclides at the site of a contaminated wound and their uptake into the transfer compartment, has been combined with the ICRP element-specific systemic models for those radionuclides to derive dose coefficients for intakes via contaminated wounds. These coefficients can be used to generate derived regulatory guidance (i.e., the activity in a wound that would result in an effective dose of 20 or 50 mSv, or in some cases, a organ-equivalent dose of 500 mSv) and clinical decision guidance (i.e., activity levels that would indicate the need for consideration of medical intervention to remove activity from the wound site, administration of decorporation therapy or both). Data are provided for 38 radionuclides commonly encountered in various activities such as nuclear weapons, fuel fabrication or recycling, waste disposal, medicine, research, and nuclear power. These include 3H, 14C, 32P, 35S, 59Fe, 57,58,60Co, 85,89,90Sr, 99mTc, 106Ru, 125,129,131I, 134,137Cs, 192Ir, 201Tl, 210Po, 226,228Ra, 228,230,232Th, 234,235,238U, 237Np, 238,239,240,241Pu, 241Am, 242,244Cm, and 252Cf.


Assuntos
Doses de Radiação , Radioisótopos/farmacocinética , Ferimentos e Lesões/metabolismo , Humanos , Rádio (Elemento)/farmacocinética , Tecnécio/farmacocinética , Tório/farmacocinética
15.
Cancer Sci ; 101(2): 336-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19917057

RESUMO

Exposure to internally deposited radionuclides is known to induce malignant tumors of various histological types. Thorotrast, a colloidal suspension of radioactive Thorium dioxide ((232)ThO(2)) that emits alpha-particles, was used as a radiographic contrast during World War II. Thorotrast is known to induce liver tumors, particularly intrahepatic cholangiocarcinoma (ICC) and angiosarcoma (AS), decades after injection. Therefore, patients injected with Thorotrast comprise a suitable study group to understand biological effects of internal ionizing radiation injury. Autoradiography and X-ray fluorescence spectrometry (XRF) were carried out on non-tumorous liver sections from Thorotrast-induced ICC (T-ICC) and Thorotrast-induced AS (T-AS). Autoradiography revealed that the slope of the regression line of the number of alpha tracks for the amount of deposited Thorium ((232)Th) was higher in non-tumorous parts of the liver with T-ICC than those with T-AS. XRF showed that the intensity ratio of Radium (Ra) to Thorium (Th) in non-tumorous liver tissue with T-ICC was significantly higher than that with T-AS. Furthermore, the mean (228)Ra/(232)Th radioactivity ratio at the time of death calculated was also significantly higher in T-ICC cases than in T-AS cases. These suggest that the metabolic behavior of radionuclides such as relocation and excretion, as well as the content of deposited radionuclides, is a major factor in determining the histological type of Thorotrast-induced liver tumors.


Assuntos
Neoplasias Hepáticas/etiologia , Rádio (Elemento)/farmacocinética , Dióxido de Tório/efeitos adversos , Tório/farmacocinética , Adulto , Partículas alfa , Autorradiografia , Transporte Biológico , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Doses de Radiação , Espectrometria por Raios X
16.
Radiats Biol Radioecol ; 49(2): 172-8, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19507685

RESUMO

The analysis of natural radionuclide (226Ra) contamination and tundra vole (Microtus oeconomus Pall.) relative number (from the sixties of 20-th century to 2007) reveals the impotent role of murine rodents in radionuclide migration. As a result of their pawing and of radionuclides carry-over by plants on the soil surface since the beginning of 1990 to present time the increase of 226Ra content in animals from control and radioactive plots have been ascertain. In the plots under study tundra vole number was half as much from 1993 to 2007. Simultaneous rotation of population cycle stages noticed in the control plot and in the plot with radium contamination, and long periods of low number was recorded in the plot with radium and thorium contamination, which are typical for border and impact populations.


Assuntos
Arvicolinae/crescimento & desenvolvimento , Monitoramento de Radiação/métodos , Poluentes Radioativos/análise , Rádio (Elemento)/análise , Animais , Arvicolinae/metabolismo , Interpretação Estatística de Dados , Dinâmica Populacional , Poluentes Radioativos/farmacocinética , Rádio (Elemento)/farmacocinética , Federação Russa , Tório/análise , Tório/farmacocinética , Urânio/análise , Urânio/farmacocinética
17.
Bioresour Technol ; 100(1): 208-10, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18614355

RESUMO

The objective of the work was to evaluate the biosorption of thorium by the seaweed Sargassum filipendula in a dynamic system. Different bed depths were tested with the purpose of evaluating the critical bed depth for total uptake of the radioactive element. Several bed depths were tested, ranging from 5.0 to 40.0 cm. Bed depths tested presented distinct capacities to accumulate thorium. An increase in biosorption efficiency was observed with an increase in bed depth. The 30.0 cm bed produced an effluent still containing detectable levels of thorium. The critical bed depth suitable for a complete removal of thorium by S.filipendula biomass was equal to 40.0 cm.


Assuntos
Reatores Biológicos , Desenho Assistido por Computador , Modelos Biológicos , Sargassum/metabolismo , Tório/farmacocinética , Poluentes Radioativos da Água/farmacocinética , Biodegradação Ambiental , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento
18.
Int J Radiat Oncol Biol Phys ; 72(1): 186-92, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18722269

RESUMO

PURPOSE: To determine the relative biologic effects (RBE) of alpha-particle radiation from 227Th-rituximab and of beta-radiation from 90Y-tiuexetan-ibritumomab (Zevalin) compared with external beam X-radiation in the Raji lymphoma xenograft model. METHODS AND MATERIALS: Radioimmunoconjugates were administered intravenously in nude mice with Raji lymphoma xenografts at different levels of activity. Absorbed dose to tumor was estimated by separate biodistribution experiments for 227Th-rituximab and Zevalin. Tumor growth was measured two to three times per week after injection or X-radiation. Treatment-induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm3, respectively, was used as an end point. RESULTS: The absorbed radiation dose-rate in tumor was slightly more than 0.1 Gy/d for the first week following injection of 227Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days after injection. For treatment with Zevalin the maximum dose-rate in tumor was achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01 Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for 227Th-rituximab and between 1 and 1.3 for Zevalin. CONCLUSIONS: Both at low doses and low-dose-rates, the 227Th-rituximab treatment was more effective per absorbed radiation dose unit than the two other treatments. The considerable effect at low doses suggests that the best way to administer low-dose-rates, alpha-emitting radioimmunoconjugates is via multiple injections.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoconjugados/uso terapêutico , Eficiência Biológica Relativa , Tório/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Partículas alfa/uso terapêutico , Animais , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Murinos , Partículas beta/uso terapêutico , Relação Dose-Resposta à Radiação , Feminino , Meia-Vida , Imunoconjugados/farmacocinética , Linfoma de Células B/metabolismo , Linfoma de Células B/radioterapia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Nus , Radioimunoterapia/métodos , Rituximab , Tório/farmacocinética , Transplante Heterólogo , Radioisótopos de Ítrio/farmacocinética
19.
Aquat Toxicol ; 88(4): 250-6, 2008 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-18571249

RESUMO

The objective of this study was to evaluate the effect of thorium (Th) bioaccumulation on the metabolism of silver catfish (Rhamdia quelen) through biochemical parameters of the muscle (glycogen, glucose, lactate, protein, and ammonia). In addition, lipidic peroxidation levels (TBARS), catalase (CAT) and glutathione-S-transferase (GST) in the gills and in hepatic and muscular tissues were also analyzed. Cytogenetic parameters were studied through the evaluation of nuclear abnormalities in red blood cells. Silver catfish juveniles were exposed to different waterborne Th levels (in microg L(-1)): 0 (control), 25.3+/-3.2, 69.2+/-2.73, 209.5+/-17.6, and 608.7+/-61.1 for 15 days. The organs that accumulated the highest Th levels were the gills and skin. The increase of waterborne Th concentration corresponded to a progressive increase of Th levels in the gills, liver, skin and kidneys, with the highest accumulation in the gills and skin. Metabolic intermediates in the muscle were altered by Th exposure, but no clear relationship was found. CAT and GST activities in the hepatic and muscular tissues of this species suggest that the enzymatic activities can be stimulated at the lowest Th levels and inhibited at the higher levels (mainly in 608.7 microg L(-1)). The results of the cytogenetic assay contribute to this hypothesis because the higher toxicity in blood samples was found in juveniles exposed to 69.2 and 209.5 microg L(-1) Th.


Assuntos
Peixes-Gato/metabolismo , Músculo Esquelético/metabolismo , Tório/farmacocinética , Amônia/metabolismo , Análise de Variância , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glucose/metabolismo , Glutationa Transferase/metabolismo , Glicogênio/metabolismo , Ácido Láctico/metabolismo , Testes para Micronúcleos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tório/sangue
20.
Radiat Prot Dosimetry ; 127(1-4): 64-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17611198

RESUMO

Some beaches in the south of France present high levels of natural radioactivity mainly due to thorium (Th) and uranium (U) present in the sand. Risk assessment after internal exposure of members of the public by either inhalation or ingestion of black sand of Camargue was performed. This evaluation required some information on the human bioavailability of U and Th from this sand. In vitro assays to determine the solubility of U, Th and their progeny were performed either in simulated lung fluid, with the inhalable fraction of sand, or in both simulated gastric and intestinal fluids with a sample of the whole sand. The experimental data show that the bioavailability of these radionuclides from Camargue sand is low in the conditions of the study. Prospective dose assessment for both routes of intake show low risk after internal exposure to this sand.


Assuntos
Carga Corporal (Radioterapia) , Exposição Ambiental/análise , Modelos Biológicos , Medição de Risco/métodos , Dióxido de Silício/farmacocinética , Poluentes Radioativos do Solo/farmacocinética , Tório/farmacocinética , Urânio/farmacocinética , Simulação por Computador , França , Humanos , Monitoramento de Radiação/métodos , Fatores de Risco , Dióxido de Silício/análise , Poluentes Radioativos do Solo/análise , Tório/análise , Urânio/análise , Contagem Corporal Total
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