A principal finalidade deste estudo foi avaliar a dose efetiva recebida pelos profissionais de saúde no setor de hemodinâmica de um hospital universitário, na cidade de São Paulo. Para delinear o perfil dos profissionais de saúde foi utilizado um questionário auto-aplicável considerando as variáveis sociodemográficas e variáveis relacionadas ao trabalho em presença de radiação ionizante. A avaliação das doses ocupacionais foi realizada por meio de consulta aos históricos de dose individual do banco de dados da instituição, durante os anos de 2000 a 2009. Um total de 240 registros foi avaliado, envolvendo 38 profissionais ativos (2009), de diferentes categorias profissionais, entre elas, médicos, enfermeiros, tecnólogos em radiologia e auxiliares de enfermagem. As doses efetivas anuais foram comparadas com os limites estabelecidos pelas autoridades regulatórias nacionais. Com base nas doses recebidas e registradas durante o período estudado, foram selecionados cinco médicos para usar mais um dosímetro termoluminescente (em caráter experimental) na mão esquerda, durante a realização dos procedimentos de hemodinâmica. Além disso, foram averiguados os procedimentos de radioproteção adotados pelos profissionais de saúde da instituição estudada. Este estudo permitiu traçar o perfil da equipe médica que integra o serviço de hemodinâmica assim como conhecer a distribuição de suas doses em relação aos limites ao longo dos anos. / The purpose of this study was to evaluate the dose received by health professionals in the hemodynamic sector of a university hospital in São Paulo city. A self-applied questionnaire was used to delineate the profile of health professionals, taking into account sociodemographic variables and variables related to the work with ionizing radiation. The assessment of occupational doses was performed by consulting of the individual dose records of the institution database from 2000 to 2009. A total of 240 records was evaluated, corresponding to 38 active professionals (2009), divided in different professional category: physician, nurses, radiologic technologists and nursing assistants. The annual doses were compared with the limits established by national regulatory authorities. Based on the effective doses received and recorded during the studied period, experimental measures were performed with TL dosimeters in five physicians to evaluate the equivalent dose, in the left hand, during hemodynamic procedures. In addition, the radioprotection measures adopted by health professionals were verified. This study allowed delineating the profile of medical staff that integrates the hemodynamic service as well as knowing the distribution of their doses in relation to limits over the years.

A principal finalidade deste estudo foi avaliar a dose efetiva recebida pelos profissionais de saúde no setor de hemodinâmica de um hospital universitário, na cidade de São Paulo. Para delinear o perfil dos profissionais de saúde foi utilizado um questionário auto-aplicável considerando as variáveis sociodemográficas e variáveis relacionadas ao trabalho em presença de radiação ionizante. A avaliação das doses ocupacionais foi realizada por meio de consulta aos históricos de dose individual do banco de dados da instituição, durante os anos de 2000 a 2009. Um total de 240 registros foi avaliado, envolvendo 38 profissionais ativos (2009), de diferentes categorias profissionais, entre elas, médicos, enfermeiros, tecnólogos em radiologia e auxiliares de enfermagem. As doses efetivas anuais foram comparadas com os limites estabelecidos pelas autoridades regulatórias nacionais. Com base nas doses recebidas e registradas durante o período estudado, foram selecionados cinco médicos para usar mais um dosímetro termoluminescente (em caráter experimental) na mão esquerda, durante a realização dos procedimentos de hemodinâmica. Além disso, foram averiguados os procedimentos de radioproteção adotados pelos profissionais de saúde da instituição estudada. Este estudo permitiu traçar o perfil da equipe médica que integra o serviço de hemodinâmica assim como conhecer a distribuição de suas doses em relação aos limites ao longo dos anos. / The purpose of this study was to evaluate the dose received by health professionals in the hemodynamic sector of a university hospital in São Paulo city. A self-applied questionnaire was used to delineate the profile of health professionals, taking into account sociodemographic variables and variables related to the work with ionizing radiation. The assessment of occupational doses was performed by consulting of the individual dose records of the institution database from 2000 to 2009. A total of 240 records was evaluated, corresponding to 38 active professionals (2009), divided in different professional category: physician, nurses, radiologic technologists and nursing assistants. The annual doses were compared with the limits established by national regulatory authorities. Based on the effective doses received and recorded during the studied period, experimental measures were performed with TL dosimeters in five physicians to evaluate the equivalent dose, in the left hand, during hemodynamic procedures. In addition, the radioprotection measures adopted by health professionals were verified. This study allowed delineating the profile of medical staff that integrates the hemodynamic service as well as knowing the distribution of their doses in relation to limits over the years.

Proton therapy facilities, as other industrial applications using ionizing radiations, are confronted to radioprotection problems and seek to mitigate the undesirable effects. The aim of this thesis is to study the IBA compact proton therapy center, the Proteus®One in this radioprotection context. The compactness of this system implies important radioprotection issues, mainly the concrete shielding activation where a model allowing to predict and characterize the impact of secondary radiations on the system is required. Numerical simulations using Monte Carlo methods are used and in particular, a benchmark between different existing software has been carried out to validate the use of the Geant4 software in this work. The first part of this thesis focuses on the design of the structural shielding taking into account neutron sources in the model. In particular, the concept of neutron-equivalent source is introduced. In this framework, the quantity and the localization of the generated nuclear waste in concrete are determined. The second part of the work investigates the beam properties and its interactions with matter along the transport beamline. After the analysis of the existing system, a new degrader, which is one of the critical elements for the emission of secondary radiations and for the performances of the device, is proposed. Comparisons between existing (aluminium, graphite, beryllium) and novel (boron carbide and diamond) degrader materials are provided and evaluated against semi-analytical models of multiple Coulomb scattering. The use of diamond with a geometry adaptation allows beam emittance reduction and beam transmission increase. The third part of this thesis considers a complete 3D model of the Proteus®One system. It contributes to acquire a detailed knowledge of the beam properties inside the beamline. This model is validated with experimental data and the assumption of neutron-equivalent source is verified. Finally, maps of proton and neutron interactions are generated to provide a complete mapping of the secondary radiations in the system. These maps can be used to determine dosimetric or radioprotection quantities. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished

Ce travail s'inscrit dans un programme de recherche visant à synthétiser de nouveaux composés organiques et phosphorés possédant un rapport activité/toxicité convenable. Pour cela, nous avons réalisé la synthèse de nouveaux motifs N-substitués du benzothiazole et du thiadiazole tels que des thiols, aminothiols, acides thiosulfoniques et phosphorothioates. Tous ces composés ont été caractérisés physico-chimiquement par spectroscopie RMN (proton, carbone, phosphore, 2D), par spectrométrie de masse, analyse élémentaire et pour certains d'entre eux par diffraction des rayons X. L'activité de la plupart des composés a été évaluée par des tests in vitro. Les résultats expérimentaux ont été confirmés par des calculs théoriques de DFT visant à étudier le mécanisme de capture des radicaux libres par nos composés. D'autre part, une étude de relation structure activité (QSAR) a été réalisée. Les résultats nous ont permis d'élaborer un modèle permettant d'établir une relation structure-activité.

Reproduction de : Thèse de doctorat : Histoire moderne et contemporaine : Lyon 2 : 2003. / Titre provenant de l'écran-titre. Bibliogr.. Index.

Harmful substances polluting the environment, including ionizing radiation, and an unhealthy lifestyle are responsible for the increased incidence of cancer. The projected outlook for the next ten to twenty years suggests an increase of 63% in newly diagnosed cases of cancer annually. Radiotherapy is an important component of cancer treatment, given approximately to 50% of all cancer patients. Despite ongoing advances in the methods of radiotherapy, quality of life continues to be lowered as a result of the radiation treatment. Novel strategies towards improvement need to be adapted, such as the use of radioprotective substances. The goal of this thesis is to synthesize novel radioprotective agents based on the 1-(2- hydroxyethyl)piperazine moiety targeting the intrinsic apoptotic pathway, therefore protecting healthy tissue from ionizing radiation.

Le travail décrit dans cette thèse porte sur l’évaluation du mode d’exposition externe et interne au xénon-133. Ce radionucléide est un des principaux produits de fission du combustible des réacteurs nucléaires. En cas de défaut de gaine combustible, le xénon-133 peut potentiellement exposer le personnel lors de ses interventions dans le bâtiment réacteur. En dosimétrie, les simulations Monte-Carlo sont des outils adaptés pour simuler le transport des rayonnements ionisants dans la matière. A partir des critères de radioprotection actuels, nous avons développé de nouvelles méthodes afin d’améliorer notre compréhension de l’exposition externe et interne auxénon-133 à l’intérieur d’un bâtiment réacteur. Ces nouvelles approches sont basées sur l’utilisation d’un fantôme anthropomorphe, d’une géométrie réaliste de bâtiment réacteur, de simulations Monte-Carlo GEANT4 et de modèles en compartiments. L’exposition externe dans un bâtiment réacteur a été menée en retenant un scénario d’exposition réaliste et conservatif. Nous avons quantifié le débit de dose efficace et le débit de dose équivalente au cristallin. L’exposition interne se produit lorsque le xénon-133 est inhalé. Les poumons sont les premiers organes exposés par l’inhalation du xénon-133, leur débit de dose équivalente a été quantifié. Un modèle biocinétique a été utilisé pour évaluer l’exposition interne au xénon-133. Cette thèse a permis de quantifier les grandeurs dosimétriques liées aux modes d’exposition externe et interne au xénon-133, d’étudier l’impact des changements de limites dosimétriques introduits par la Commission Internationale de Radioprotection prochainement retranscrits dans la réglementation française, et de comprendre la cinétique du xénon-133 dans le corps humain. Nous avons montré que les grandeurs dosimétriques sont nettement inférieures aux limites dosimétriques de la réglementation actuelle et future. / The work described in this thesis focuses on the external and internal dose assessment to xenon-133. During the nuclear reactor operation, fission products and radioactive inert gases, as ¹³³Xe, are generated and might be responsible for the exposure of workers incase of clad defect.Particle Monte Carlo transport code is adapted inradioprotection to quantify dosimetric quantities.The study of exposure to xenon-133 is conducted byusing Monte-Carlo simulations based on GEANT4, ananthropomorphic phantom, a realistic geometry of thereactor building, and compartmental models.The external exposure inside a reactor building isconducted with a realistic and conservative exposurescenario. The effective dose rate and the eye lensequivalent dose rate are determined by Monte-Carlosimulations. Due to the particular emission spectrum ofxenon-133, the equivalent dose rate to the lens of eyesis discussed in the light of expected new eye doselimits.The internal exposure occurs while xenon-133 isinhaled. The lungs are firstly exposed by inhalation, andtheir equivalent dose rate is obtained by Monte-Carlosimulations. A biokinetic model is used to evaluate theinternal exposure to xenon-133.This thesis gives us a better understanding to thedosimetric quantities related to external and internalexposure to xenon-133. Moreover the impacts of thedosimetric changes are studied on the current andfuture dosimetric limits. The dosimetric quantities arelower than the current and future dosimetric limits.

Après l’incorporation de radionucléides dans l’organisme, l’imagerie quantitative en médecine nucléaire et l’anthroporadiométrie sont utilisés pour quantifier l’activité retenue. L’étalonnage de ces systèmes in vivo peut être amélioré afin de tenir en compte de la variabilité individuelle. En vue d’optimiser la mesure de l’activité retenue, des fantômes d’étalonnage innovants ont été réalisés par impression 3D. L’infographie 3D a été utilisée pour la conception, en parallèle avec un travail d’ingénierie permettant l’inclusion de radionucléides et l’adaptation aux besoins des utilisateurs. Un jeu de fantômes thyroïdiens adapté à l’âge a été développé et utilisé pour améliorer la mesure anthroporadiométrique thyroïdienne des enfants. À la suite d’une étude systématique, les coefficients d’étalonnage des installations de routine et de crise de l’IRSN ont été déterminés pour l’adulte et les enfants de 5, 10 et 15 ans. Un fantôme thyroïdien pathologique a été développé en plus du jeu de fantômes thyroïdiens dédié à la crise pour améliorer la mesure de fixation thyroïdienne en médecine nucléaire. Une étude multicentrique a été réalisée pour optimiser l’étalonnage afin de mieux personnaliser le traitement des pathologies bénignes de la thyroïde. Pour l’anthroporadiométrie pulmonaire, une famille de fantômes de poitrine a été développée pour améliorer la surveillance des travailleuses du nucléaire. Finalement, ce travail de recherche a permis de développer des fantômes adaptés aux besoins et de démontrer leur utilité pour la quantification de l’activité en dosimétrie interne. / Following the incorporation of radionuclides in the body, quantitative imaging in nuclear medicine and in vivo spectrometry measurements are used to quantify the retained activity. The calibration of these in vivo systems can be improved to take account of individual variability. To optimize the measurements of the activity retained, innovative calibration phantoms were created and manufactured by 3D printing. 3D computer graphics were used for the design, coupled with an engineering work allowing the inclusion of radionuclides and the fit to users’ needs. A set of age-specific thyroid phantoms has been developed and used to improve the thyroid in vivo measurement of children. Following a systematic study, the calibration coefficients for IRSN emergency and routine installations were determined for adults and 5, 10 and 15 year old children. A pathological thyroid phantom has been developed in addition to the set of thyroid phantoms dedicated to the emergency to improve the thyroid uptake measurement in nuclear medicine. A multicentre study was carried out to optimize the calibration so that treatment of thyroid benign diseases moves towards a better personalization. For lung in vivo measurement, a set of breast phantoms has been developed to improve the monitoring of female workers. Finally, this research work has allowed developing several phantoms adapted to the needs and their usefulness was proven for the quantification of the activity in internal dosimetry.

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH2), dextran T10-polyethylene glycol (DT10-PEG), dextran T10-sulfobetaine (DT10-SB) and poly(acrylic acid) (PAA), and compared to uncoated. 89Zr was incorporated into CONPs for positron emission tomography (PET) imaging and ex vivo tissue analysis in tumor bearing mice. Compared to uncoated [89Zr]CONPs, coated [89Zr]CONPs showed improved biodistribution, including significantly enhanced renal clearance of PAA- [89Zr]CONPs. The toxicity of CONPs was evaluated in vitro and in vivo, with low toxicity at therapeutic doses. After clinically mimetic radiation therapy, pre-treatment of mice with coated and uncoated CONPs showed greater than 50% reduction of cell death in normal colon tissue, comparable to the clinically available radioprotective drug amifostine. Tumor control after irradiation of spontaneous colon tumors was unchanged with PAA-CONP pre-treatment, while citrate, DT10-PEG, and uncoated CONP pre-treatment had slightly less tumor control. Xenograft tumors were irradiated after pH normalizing treatment with sodium bicarbonate and PAA-CONP pre-treatment. Treatment of these tumors showed slightly less tumor control than irradiation alone or PAA-CONP plus irradiation, demonstrating that the acidic pH of the tumor microenvironment may be the basis of preventing CONPs’ radioprotective properties in tumor. These studies show that, among the variations of CONPs tested, PAA-CONP shows the most promise for its good biodistribution and quick clearance, low toxicity, ability to protect normal tissue, and lack of protection of tumor, meeting all the criteria set forth for an ideal radioprotective drug. Further studies on the effects of pH on CONPs actions may further elucidate their mechanisms of action, advancing them as a candidate for use as a radioprotective drug during radiation therapy.

O presente trabalho tratou do estudo dos riscos apresentados pelos radioisótopos após serem submetidos aos efeitos da detonação de um artefato explosivo. O estudo permitiu a obtenção de dados baseados em pesquisas bibliográficas, documentais, cálculos e softwares, possibilitando análises das consequências resultantes de artefatos explosivos contendo radioisótopos. O objetivo deste trabalho foi a obtenção de conhecimentos quanto à potencialidade destrutiva do explosivo denominado emulsão, composto principalmente por nitrato de amônia, bem como das propriedades do cobalto, iodo e do irídio que farão parte da carga destes explosivos. Supomos que à emulsão fossem acrescentadas as atividades de 1,5.102 TBq de cobalto-60, 3,7.10-3 TBq de iodo-131 e 3,7 TBq de irídio-192 que são suas atividades representativas em radioterapia, medicina nuclear e gamagrafia respectivamente. Avaliamos a progressão da pluma radioativa a partir do epicentro da explosão, possibilitando análises dos valores das doses, da distribuição e do alcance, a partir do epicentro, dos radioisótopos estudados. A simulação da progressão da pluma radioativa foi realizada por cálculos e simulação computacional fazendo uso dos programas Blast/FX Explosive Effects Analysis Software e The HotSpot Health Physics Codes - Version 2.07.2. No trabalho só foram estudadas as doses resultantes da exposição externa considerando que todo material radioativo volatizou. Foi deixado para estudos futuros calcular as doses internas e no pulmão bem como as doses resultantes de estilhaços radioativos produzidos na explosão. / This job devotes to the study of the radioisotopes risks, after the effects of an explosion of an explosive device. This study developes data based on bibliographies, documents, calculation and also software, and as a result, could provide analysis of an explosive device blast with radioisotopes. The purpose of this work is to provide knowlegde about the potencial destructive result of a blast of an explosive called emulsion, made with ammonia nitrate, and also with cobalt properties, iodine and iridium of a explosive charge. To this emulsion were added activities of 1,5.102 TBq of Cobalt-60, 3,7.10-3 TBq of iodine-131 and 3,7 TBq of iridium-192. Such activities are seen in radioterapy, nuclear medicine and gamagraphy. It could consider the radioative plume progress from the blast epicenter, in order to analyse the value of the dose, the distribution and the distance from the epicenter of the radioisotope studied. The simulation of the radioative plume progress was made with calculation and computer software, such as Blast/FX Explosive effects analysis software and The Hotspot health physics Codes version 2.07.2. In this study was only possible to check the doses from the external effects, to consider the fact that all radioative material result in volatization. It´s important to say that we left for future studies the calculation of the internal doses and inside the lung, and also the doses of the radioative shrapnel from the blast.