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Orientador: Marco Antônio Rodrigues Fernandes / Resumo: O uso de fontes de radiações ionizantes tem sido cada vez mais presente nas diversas atividades técnico-científicas. Os cuidados e os benefícios da prática já são bastante conhecidos e difundidos na área da medicina de humanos, tanto no campo do diagnóstico quanto da terapia. Na área da medicina veterinária, a radioterapia vem ganhando espaço, no entanto, o uso de feixes de radiações ionizantes exige o conhecimento de legislações específicas sobre proteção radiológica e a atuação de profissionais altamente especializados. O uso seguro das práticas de radioterapia requer o dimensionamento de blindagens para a correta proteção dos profissionais, dos pacientes e do meio ambiente. Neste trabalho foram realizados cálculos de blindagem para dimensionamento das espessuras das barreiras de proteção à radiação para uma sala de radioterapia adequada para o uso de um equipamento de teleterapia de ortovoltagem, destinado para procedimentos de radioterapia em medicina veterinária. Foram também realizados estudos para o dimensionamento das mesmas barreiras e condições de trabalho para o uso em braquiterapia de alta e de baixa taxa de dose (BATD e BBTD), para diferentes fontes radioativas. Foram ainda desenvolvidos os cálculos para dimensionamento das paredes de um espaço localizado no interior do canil situado no prédio da Faculdade de Medicina Veterinária e Zootecnia da Unesp de Botucatu (FMVZ), visando sua adequação para a realização de procedimentos de braquiterapia de baixa de dose. Os... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of ionizing radiation surces has increased in various technical-scientific activities. The care and benefits of the practice are already well known and widespread in human medicine, both in the field of diagnosis and therapy. In the area of veterinary medicine, radiotherapy has been gaining space, however, the use of ionizing radiation beams requires the knowledge of specific legislation on radiolprotection and specialized professionals. The safe use of radiotherapy practices requires the design of shielding for the correct protection of professionals, patients and the environment. The present study calculated the dimension and thickness of the radiation protection barriers to a radiotherapy room suitable for the use of orthovoltage teletherapy equipment, destined for radiotherapy procedures in veterinary medicine. Studies were also carried out for the design of the same barriers and working conditions for use in high and low dose rate brachytherapy (HDR and LDR) for different radioactive sources. The calculations for dimensioning the walls of a dog kennel located in the school of Veterinary Medicine and Animal Science, Unesp Botucatu (FMVZ), were also developed, aiming at their adequacy for the accomplishment of dose rate brachytherapy procedures. The results showed that the thicknesses calculated for the walls of the orthovoltage radiotherapy room are sufficient for the shielding of the radiations from the sources of high and low dose rate brachytherapy. / Mestre

Au moins 60% des patients atteints de cancer vont recevoir de la radiothérapie (RT). L’efficacité de la radiothérapie dans le traitement du cancer est limitée par le phénomène de radiorésistance des cellules cancéreuses et par la toxicité des radiations sur les tissus sains. La découverte de nouveaux agents radiosensibilisants et radioprotecteurs permettrait de surmonter ces difficultés. Les modèles cellulaires 3D tels que les sphéroïdes, émergent motivés par le besoin de modèles précliniques plus proches des tumeurs in vivo. L’objectif du projet est d’optimiser un système microfluidique pour tester facilement et à faible coût des agents thérapeutiques avec la RT sur des sphéroïdes dans un contexte de repositionnement. Le système microfluidique développé permet la formation de 336 sphéroïdes homogènes en deux jours avec intervention minimale de l’utilisateur. Les sphéroïdes sont répartis dans 16 chambres de culture séparées par un système de valve magnétique pour éviter des effets bystander entre sphéroïdes irradiés et non-irradiés. Une nouvelle technique d’irradiation a été développée permettant d’exposer un système à 4 doses de radiation différentes. En tout, 4 doses de radiation et 4 concentrations d’agents thérapeutiques peuvent être testées par système. En utilisant cette approche, l’efficacité de trois agents avec la RT a été évaluée avec des tests de survie clonogénique. Nous avons démontré que le Talazoparib, un inhibiteur de PARP, radiosensibilise les cellules de sarcome de tissus mous (STS) cultivés en sphéroïdes à 2 Gy. Le système développé permet d’évaluer le potentiel d’agents thérapeutiques avec la RT et contribue à l’adoption des sphéroïdes comme modèle préclinique. / At least 60% of cancer patients will receive radiotherapy (RT) as part of their treatment. The efficacy of radiotherapy in the treatment of cancer is limited by the phenomenon of radioresistance of cancer cells and by the toxicity of radiation on healthy tissues. The discovery of new radiosensitizers and radioprotectors is essential to overcome these challenges. 3D cellular models such as spheroids emerge motivated by the need for better preclinical models. The objective of the project was to optimize a microfluidic system for easy, fast and low-cost testing of therapeutic agents with RT on spheroids. The developed microfluidic system allows the formation of 336 homogeneous spheroids in two days with minimal user intervention. The spheroids are distributed in 16 culture chambers separated by a magnetic valve system to avoid bystander effects between irradiated and unirradiated spheroids. A new irradiation technique has been developed to expose a system with 4 different radiation doses. In total, 4 radiation doses and 4 concentrations of therapeutic agents can be tested per system. Using this approach, the efficacy of three agents with RT was evaluated with clonogenic assays. Radiosensitizing properties of Talazoparib, a PARP inhibitor, on soft tissue sarcoma (STS) cells cultured as spheroids at 2 Gy were demonstrated. The developed system enables the evaluation of therapeutic agents with RT and contributes to the wide adoption of spheroids as a preclinical model.