A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens. Uma modalidade de tratamento que vem sendo bastante utilizada é a braquiterapia, que consiste na introdução de sementes com material radioativo no interior do orgão. Sementes de Iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis. As sementes em cordas poliméricas apresentam algumas vantagens, pois reduzem a taxa de migração das sementes, evento que poderia afetar a dosimetria da região e causar danos desnecessários a tecidos ou órgãos sadios. Para as sementes de Iodo-125 em cordas poliméricas, utiliza-se a poliglactina 910, (poli(ácido lático-co-ácido glicólico)) (PLGA), com cobertura de poliglactina 370 (Vicryl®). Foi proposto neste trabalho, o estudo e desenvolvimento da metodologia de síntese do biopolímero PLGA, via polimerização por abertura de anéis, assim como sua caracterização, com o propósito de utilizar o material sintetizado para fabricar um material similar ao RAPID-Strand®. Os resultados obtidos demonstram que, através da metodologia utilizada, foi possível determinar os melhores parâmetros de reação (tempo e temperatura) para o PLGA na proporção 80/20 (lactídeo/glicolídeo). Com uma temperatura de 110ºC e tempo de reação de 24h, foi possível obter 86% de rendimento, e com o aumento o tempo de reação para 72h, o rendimento é superior a 90%. Os valores de massas moleculares obtidas entre os testes, ainda são muito baixos quando comparados com os valores obtidos por outros autores na literatura (cerca de 20%). Falhas na selagem das ampolas, deixando-os vulneráveis à umidade e oxigênio, ou a falta de uma sistema eficiente de agitação podem ser possíveis explicações para estes resultados. Um reator químico adequado poderia solucionar o problema. Em relação à caracterização, as técnicas utilizadas confirmaram a estrutura esperada do polímero, e a maior proporção das unidades provenientes do dímero lactídeo, em relação ao glicolídeo. / According to World Health Organization (WHO), cancer is a leading cause of death worldwide. Prostate cancer is the second most common cancer in men. A method of radiotherapy which has been extensively used is brachytherapy, where radioactive seeds are placed inside the area requiring treatment. Iodine-125 seeds can be placed loose or stranded in bioabsorbable polymers. Stranded seeds show some advantages, since they reduce the rate of seed migration, an event that could affect the dosimetry of the prostate and cause unnecessary damage to healthy tissues or organs. For Iodine-125 stranded seeds, polyglactin 910 (poly(lactic-co-glycolic acid)) (PLGA), with a coverage of polyglactin 370 (Vicryl ®) is used. It was purposed in this dissertation, the study and development of the synthesis methodology for PLGA via ring-opening polymerization, as well as its characterization, with the objective of using the synthesized material to manufacture a material similar to RAPID Strand®. The results obtained show that it was possible to determine the optimal reaction parameters (time and temperature) for PLGA in 80/20 (lactide/glycolide) ratio. Using a temperature of 110 ° C and reaction time of 24h, a yield of 86% was obtained, and increasing the reaction time to 72 hours, the yield was higher than 90%. The molecular mass values obtained from the samples are still very low compared to those obtained by other authors in the literature (about 20%). Failures in the sealing of vials, leaving them vulnerable to moisture and oxygen, or lack of an efficient stirring system might be possible explanations for these results. A suitable chemical reactor could solve the problem. Regarding polymer characterization, all techniques used not only confirmed the expected structure of the polymer, but also showed the highest proportion of lactide units compared to to glycolide units.

Nenhuma / A braquiterapia é uma modalidade de radioterapia em que a fonte radioativa é colocada em contato com o tecido a ser tratado. Na braquiterapia intersticial são utilizadas pequenas fontes radioativas seladas, denominadas sementes. A busca por novos modelos de sementes é constante. O CDTN desenvolveu parcialmente um protótipo para tratamento de braquiterapia que consiste de uma matriz cerâmica porosa capaz de incorporar diferentes radionuclídeos. A etapa seguinte ao desenvolvimento de um novo tipo de semente consiste na sua caracterização dosimétrica, que deve ser realizada em concordância com determinados padrões internacionais. Uma metodologia prática, que utiliza filmes fotográficos foi desenvolvida em um trabalho prévio de mestrado do CDTN para caracterizar parcialmente sementes de braquiterapia e avaliar possíveis problemas que podem ocorrer nas fases iniciais do desenvolvimento de novas sementes, tais como baixa taxa de incorporação, que se traduz numa baixa dose depositada ou uma incorporação não homogênea, que resultaria numa deformação espacial do campo de radiação (anisotropia). Essa metodologia foi agora aprimorada e utilizada na obtenção das curvas de isodose de sementes de iodo-125, na obtenção da curva de calibração dos filmes e nas estimativas de dose em meios com diferentes níveis de atenuação da radiação, assim como para diferentes distribuições espaciais de sementes. Como o protótipo da semente do CDTN não foi totalmente finalizado utilizou-se, neste trabalho, como referência, uma semente comercial de iodo-125. A metodologia mostrou-se sensível, podendo ser utilizada para sementes com baixa atividade. A utilização dos filmes fotográficos permite visualizar, caso existam, problemas de incorporação do material radioativo, o que pode ocorrer até mesmo em sementes comerciais. Portanto, o método mostra-se útil para uma verificação rápida de sementes antes de serem utilizadas em pacientes. / Brachytherapy is a form of radiotherapy where a radioactive source is placed in contact with the tissue to be treated. In interstitial brachytherapy, small radioactive sealed sources are used, which are called seeds. The search for new types of seeds is constant. CDTN has partially developed a prototype for brachytherapy treatment consisting of a porous ceramic matrix capable of incorporating different radionuclides. The next step of developing a new type of seed is its dosimetric characterization, which must be performed in accordance with certain international standards. A practical methodology that uses photographic film was developed in a prior masters work accomplished at CDTN to characterize partially brachytherapy seeds and evaluate possible problems that can occur in the early stages of new seeds development, such as low incorporation rate, which translates in a low dose deposition or a inhomogeneous incorporation, resulting in a space radiation field deformation (anisotropy). This method has now been improved and used in obtaining the iodine-125 seeds isodose curves, in the the film calibration curve obtainment and dose values estimates in mediums with different radiation attenuation levels as well as different seeds spatial distributions. As the CDTNs prototype seed has not been fully finalized, in this work, it was used as reference, a commercial seed of iodine-125. The method was sensitive and can be used for seeds with low activity. The use of photographic film allows the visualization of radioactive material incorporation problems, if any, which can occur even in commercial seeds. Therefore, the method shows to be useful for a quick check of seeds before they are used in patients.

Percutaneous needle placement, a minimally invasive procedure performed dozens of millions in the U.S. each year, relies on dedicated skill and long-term training due to difficult control of needle trajectory inside tissue and mental registration of images to locations inside the patient. Inaccurate needle placement may miss cancer tumors during diagnosis or eradicate healthy tissue during therapy. MRI provides ideal procedure guidance with the merit of excellent soft tissue contrast and volumetric imaging for high spatial resolution visualization of targets and surgical tool. However, manual insertion in the bore of an MRI scanner has awkward ergonomics due to difficult access to the patient, making both training and intervention even harder. To overcome the challenges related to MRI electromagnetic compatibility and mechanical constraints of the confined close-bore, a modular networked robotic system utilizing piezoelectric actuation for fully actuated prostate biopsy and brachytherapy is developed and evaluated with accuracy study. To enhance manipulation dexterity, two kinds of steerable continuum needle robots are developed. The asymmetric tip needle robot performs needle rotation and translation control to minimize tissue deformation, and increase steering dexterity to compensate placement error under continuous MRI guidance. The MRI-guided concentric tube robot is deployed to access delicate surgical sites that are traditionally inaccessible by straight and rigid surgical tools without relying on tissue reaction force. The master-slave teleoperation system with hybrid actuation is the first of its kind for prostate intervention with force feedback. The teleoperation controller provides the feel and functionality of manual needle insertion. Fabry- Perot interferometer based fiber optic force sensor is developed for the slave manipulator to measure needle insertion force and render proprioception feedback during teleoperation.

A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens. Uma modalidade de tratamento que vem sendo bastante utilizada é a braquiterapia, que consiste na introdução de sementes com material radioativo no interior do orgão. Sementes de Iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis. As sementes em cordas poliméricas apresentam algumas vantagens, pois reduzem a taxa de migração das sementes, evento que poderia afetar a dosimetria da região e causar danos desnecessários a tecidos ou órgãos sadios. Para as sementes de Iodo-125 em cordas poliméricas, utiliza-se a poliglactina 910, (poli(ácido lático-co-ácido glicólico)) (PLGA), com cobertura de poliglactina 370 (Vicryl®). Foi proposto neste trabalho, o estudo e desenvolvimento da metodologia de síntese do biopolímero PLGA, via polimerização por abertura de anéis, assim como sua caracterização, com o propósito de utilizar o material sintetizado para fabricar um material similar ao RAPID-Strand®. Os resultados obtidos demonstram que, através da metodologia utilizada, foi possível determinar os melhores parâmetros de reação (tempo e temperatura) para o PLGA na proporção 80/20 (lactídeo/glicolídeo). Com uma temperatura de 110ºC e tempo de reação de 24h, foi possível obter 86% de rendimento, e com o aumento o tempo de reação para 72h, o rendimento é superior a 90%. Os valores de massas moleculares obtidas entre os testes, ainda são muito baixos quando comparados com os valores obtidos por outros autores na literatura (cerca de 20%). Falhas na selagem das ampolas, deixando-os vulneráveis à umidade e oxigênio, ou a falta de uma sistema eficiente de agitação podem ser possíveis explicações para estes resultados. Um reator químico adequado poderia solucionar o problema. Em relação à caracterização, as técnicas utilizadas confirmaram a estrutura esperada do polímero, e a maior proporção das unidades provenientes do dímero lactídeo, em relação ao glicolídeo. / According to World Health Organization (WHO), cancer is a leading cause of death worldwide. Prostate cancer is the second most common cancer in men. A method of radiotherapy which has been extensively used is brachytherapy, where radioactive seeds are placed inside the area requiring treatment. Iodine-125 seeds can be placed loose or stranded in bioabsorbable polymers. Stranded seeds show some advantages, since they reduce the rate of seed migration, an event that could affect the dosimetry of the prostate and cause unnecessary damage to healthy tissues or organs. For Iodine-125 stranded seeds, polyglactin 910 (poly(lactic-co-glycolic acid)) (PLGA), with a coverage of polyglactin 370 (Vicryl ®) is used. It was purposed in this dissertation, the study and development of the synthesis methodology for PLGA via ring-opening polymerization, as well as its characterization, with the objective of using the synthesized material to manufacture a material similar to RAPID Strand®. The results obtained show that it was possible to determine the optimal reaction parameters (time and temperature) for PLGA in 80/20 (lactide/glycolide) ratio. Using a temperature of 110 ° C and reaction time of 24h, a yield of 86% was obtained, and increasing the reaction time to 72 hours, the yield was higher than 90%. The molecular mass values obtained from the samples are still very low compared to those obtained by other authors in the literature (about 20%). Failures in the sealing of vials, leaving them vulnerable to moisture and oxygen, or lack of an efficient stirring system might be possible explanations for these results. A suitable chemical reactor could solve the problem. Regarding polymer characterization, all techniques used not only confirmed the expected structure of the polymer, but also showed the highest proportion of lactide units compared to to glycolide units.

As expectativas da Organização Mundial de Saúde para o ano de 2030 são que o número de mortes por câncer seja de aproximadamente 13,2 milhões, evidenciando a elevada parcela desta doença no problema de saúde mundial. Com relação ao câncer de próstata, de acordo com o Instituto Nacional do Câncer, o número de casos diagnosticados no mundo em 2012 foi de aproximadamente 1,1 milhão, enquanto que no Brasil os dados indicam a incidência de 68 mil novos casos. O tratamento deste tipo de neoplasia pode ser realizado com cirurgia (prostatectomia) ou radioterapia. Dentre a radioterapia, podemos destacar a técnica de braquiterapia, a qual consiste na introdução (implante) de pequenas fontes radioativas (sementes) no interior da próstata, onde será entregue um valor elevado de dose no volume de tratamento e baixa dose nos tecidos ao redor. No Brasil, a classe médica estima uma demanda de aproximadamente 8000 sementes/mês, sendo o custo unitário de cada semente de pelo menos U$ 26,00. A Associação Americana de Físicos na Medicina publicou alguns documentos descrevendo quais parâmetros e análises devem ser realizadas para avaliações da distribuição de dose, como por exemplo, os parâmetros Constante de taxa de dose, Função radial e Função de anisotropia. Estes parâmetros podem ser obtidos através de medidas experimentais da distribuição de dose ou por simulações computacionais. Neste trabalho foram determinados os parâmetros dosimétricos da semente OncoSeed-6711 da empresa Oncura-GEHealthcare e da semente desenvolvida pelo Grupo de Dosimetria de Fontes de Braquiterapia do Centro de Tecnologia das Radiações (CTR IPEN-CNEN/SP) por simulação computacional da distribuição de dose utilizando o código MCNP5, baseado no Método de Monte Carlo. A semente 6711 foi modelada, assim como um sistema dosimétrico constituído por um objeto simulador cúbico de 30x30x30 cm3 preenchido com água. Os valores obtidos da semente 6711 foram comparados com alguns apresentados na literatura, onde o parâmetro Constante de taxa de dose apresentou erro relativo em relação ao valor publicado no TG- 43 de 0,1%, sendo que os outros parâmetros analisados também apresentaram boa concordância com os valores publicados na literatura. Deste modo, pode-se considerar que os parâmetros utilizados nas simulações (espectro, modelagem geométrica e avaliação de resultados) estão compatíveis com outros estudos, sendo estes parâmetros também utilizados nas simulações da semente do IPEN. Considerando as análises de incerteza estatística, os valores obtidos da semente do IPEN são semelhantes aos valores da semente 6711. / Expectations of the World Health Organization for the year 2030 are that the number of cancer deaths is approximately 13.2 million, reflecting the high proportion of this disease in global health issue. With respect to prostate cancer, according to the National Cancer Institute, the number of cases diagnosed worldwide in 2012 was approximately 1.1 million, while in Brazil the data demonstrated the incidence of 68,000 new cases. The treatment of cancer can be performed with surgery (prostatectomy) or radiation therapy. Among radiotherapy, we can highlight the brachytherapy technique, which consists in the introduction of small radioactive sources (seeds) within the prostate, which is delivered a high dose value in the treatment volume and low dose in the surrounding tissues. In Brazil, the medical profession estimates a demand of approximately 8000 seeds / month, and the unit cost of each seed at least US $ 26.00. The AAPM protocol TG-43 recommend the dose-rate constant, radial dose function and anisotropy function for dosimetric analysis LDR brachytherapy seeds. In this work, Monte Carlo simulations were performed in order to assess the dosimetric parameters of the OncoSeed-6711, manufactured by Oncura-GEHealthcare, and a seed developed by Radiation Technology Center, using the MCNP5 code. A 6711 seed, anIPEN seed and the 30x30x30cm3phantom filled with water were modeled to simulatethe dose distribution. The 6711 seed parameters were compared with literature, and the results presented relative error less than 0.1% for Λ. In comparison with the 6711 seed, the IPEN model seed dosimetric parameters were similar, account the statistical uncertainty.

Os procedimentos braquiterápicos atuais seguem as diretrizes apresentadas no protocolo da AAPM TG - 43, introduzido em 1995, que define a metodologia de cálculo de dose ao redor de fontes encapsuladas. Este protocolo, dentre outras considerações, adota a água como meio dosimétrico padrão e desconsidera a composição dos tecidos, densidades e dimensões do paciente nas estimativas de dose absorvida. Com o objetivo de realizar os cálculos de dose em condições mais próximas à realidade, a AAPM publicou em 2012 o TG-186, que introduz os algoritmos de cálculos de dose baseados em modelos na braquiterapia (MBDCA- model-based dose calculation algorithm). Estes algoritmos são capazes de considerar as complexidades descritas acima, além de permitirem estimativas de dose diretamente nos tecidos biológicos. Apesar deste advento, ainda há controvérsia sobre a melhor forma de se reportar a dose absorvida, com pontos favoráveis tanto para estimativas de dose na água, quanto nos tecidos. Esta tese se insere dentro deste contexto, buscando a correlação entre todo o conhecimento previamente adquirido baseado em água com os modernos algoritmos de cálculo de dose. A relação entre a dose na água e no meio é realizada através da teoria da cavidade, que assume que a fluência dos fótons na água e no meio é idêntica. Parte dos objetivos do presente trabalho foi avaliar a fluência energética de fótons em diferentes meios irradiados com fontes braquiterápicas de energias baixas (<50,0 keV), propondo uma forma eficiente de correlacionar a dose na água e no meio em situações nas quais a fluência dos fótons é relevante. Avaliou-se a dose absorvida na água e em diferentes tecidos humanos, para quantificar fatores de conversão entre as estimativas de dose, simulados por Monte Carlo. Para validar tais fatores foi proposta uma metodologia experimental com o uso de um objeto simulador, desenvolvido especificamente para a realização deste trabalho e com capacidade de medir os efeitos da heterogeneidade do meio utilizando doses absorvidas em dosímetros termoluminescentes. As correções baseadas na fluência energética obtidas neste estudo, quando necessárias, são capazes de correlacionar a dose absorvida no tecido e na água com uma precisão melhor do que 0,5 % nos casos mais críticos (ex. osso). Os fatores de conversão calculados mostraram que a dose absorvida na água subestima a dose absorvida no osso em até 80 %, mas superestima a dose no tecido adiposo em aproximadamente 75 %, ressaltando a necessidade de se considerar a composição e a densidade do meio nas estimativas de dose. Os resultados experimentais permitiram validar os fatores de conversão de dose simulados com diferenças máximas de 8,5 %, entre os valores experimentais e simulados. Todos os resultados obtidos comprovaram que a estimativa da dose absorvida em procedimentos braquiterápicos com baixas energias diferem significativamente quando realizadas na água e nos tecidos biológicos, evidenciando a necessidade do uso de algoritmos que considerem a heterogeneidade do meio. Tais resultados também enfatizaram a necessidade de se considerar com precisão a composição do corpo, uma vez que variações nas composições médias dos tecidos podem afetar as estimativas dosimétricas e aumentar as incertezas dos resultados. / Brachytherapy treatments are commonly performed using the American Association of Physicists in Medicine (AAPM) Task Group report TG-43, introduced in 1995, which defines the formalism for the calculation of absorbed dose to water, and neglects human tissue densities, material compositions, body interfaces, body shape and dose perturbations from applicators. In order to perform dose calculations in conditions closer to reality, the AAPM published in 2012 the TG-186, which introduces the model-based dose calculation algorithm (MBDCA) in brachytherapy. These algorithms are able to consider the complexities described above, in addition, it allows dose estimates directly into biological tissues. Despite the advent, the best way to report the absorbed dose is still a matter of debate, with favourable points for both water and tissue absorbed dose estimates. The present thesis is inserted within this context, searching for the correlation between all previously acquired knowledge based in absorbed dose to water with the absorbed dose calculated using modern MBDCA. The correlation between the doses in water and the doses in tissue is performed through the cavity theory, which generally assumes that the fluence of the photons in water and in tissue are identical. Part of the purpose of the present work was to evaluate the energy-fluence of photons in different medium irradiated with low energy brachytherapy sources (<50,0 keV), proposing an efficient way to correlate absorbed dose to water and absorbed dose to tissue in brachytherapy in situations in which the fluence of the photons is relevant. In addition to this objective, the dose absorbed in water and in different human tissues was evaluated to quantify conversion factors between these dose estimates, simulated by Monte Carlo. To validate such factors, an experimental methodology was proposed in a phantom with the capacity to quantify the effects of the heterogeneity of the medium measuring absorbed doses in thermoluminescent dosimeters. The energy-fluence based corrections given in this work, when necessary, are able to correlate the absorbed dose to tissue and absorbed dose to water with an accuracy better than 0.5 % in the most critical cases (e.g.: bone tissue). The calculated conversion factors showed that the absorbed dose to water underestimates the absorbed dose to bone by up to 80 % but overestimates the dose in adipose tissue by approximately 75 %, emphasizing the need to consider the composition and the density of tissue in the dose estimates. The experimental results allowed validating the simulated conversion factors with maximum differences of 8.5 % between the experimental and simulated dose values. All the results obtained showed that the estimation of the dose absorbed in low energy brachytherapy procedures differ significantly when performed in water and in biological tissues, evidencing the necessity of using MBDCA. These results also emphasized the need to accurately consider tissue composition, since the smallest variations in tissue compositions may affect dosimetric estimates and increase uncertainties of the results.

Ce travail de thèse a pour but de développer et de caractériser de nouveaux systèmes d'assurance qualité en curiethérapie, à base de sondes dosimétriques en Nitrure de Gallium (GaN). L'étude comprend d'une part la caractérisation et la simulation du transducteur GaN et de la sonde dosimétrique, et d'autre part la mise en œuvre et les tests de 2 systèmes d'assurance qualité.Les propriétés de radioluminescence du transducteur GaN ont été étudiées afin d'optimiser le signal dosimétrique des sondes. La sonde dosimétrique encapsulant un petit volume de cristal GaN a ensuite été caractérisée en vue de son intégration dans des systèmes d'assurance qualité. Des simulations Monte Carlo sur la sonde GaN ont également été effectuées et comparées aux mesures.Pour l'assurance qualité en curiethérapie, nous avons proposé une méthode utilisant plusieurs sondes GaN, pour permettre de déterminer en temps réel les principaux paramètres physiques d'un projecteur de source : la position, le temps de pause et l'activité de la source. Nous avons conçu et réalisé deux prototypes de systèmes d'assurance qualité mettant en œuvre cette méthode : un fantôme instrumenté pour le contrôle prétraitement et un applicateur gynécologique instrumenté pour le contrôle pendant le traitement. Ces deux prototypes ont été testés en conditions cliniques, et leurs principales caractéristiques sont satisfaisantes. Ils répondent aux besoins applicatifs et offrent une perspective intéressante pour de nouveaux outils de contrôle qualité en curiethérapie / This work aims to develop and characterize novel quality assurance systems based on Gallium Nitride (GaN) dosimeter probe for brachytherapy. It includes characterization and simulation studies of the GaN transducer and of the dosimeter probe as well as the implementation and testing of two quality assurance system prototypes.The radioluminescence properties of the GaN transducer have been studied for optimization of the dosimeter response. Characterization studies of dosimeter probes incorporating miniaturized GaN transducers have been carried out in the frame of the quality assurance systems development. Monte Carlo simulations of the GaN probe under irradiation has also been performed and compared with measurements.A method which processes simultaneously the output signals from several GaN probes has been proposed for real time determination of the projector’s physical parameters (dwell position, dwell time and activity of the source). Two quality assurance system prototypes implementing this method have been designed and fabricated: an instrumented phantom for pre-treatment quality assurance and an instrumented gynecological applicator for in vivo quality control. These two prototypes have been tested and evaluated in clinical conditions and their main characteristics are satisfactory. Both systems are in line with the application requirements and offers new perspectives for quality assurance in brachytherapy

Developing radiation delivery systems for optimisation of absorbed dose to the target without normal tissue toxicity requires advanced calculations for transport of radiation. In this thesis absorbed dose and fluence in different radiotherapy applications were calculated by using Monte Carlo (MC) simulations. In paper I-III external neutron activation of gadolinium (Gd) for intravascular brachytherapy (GdNCB) and tumour therapy (GdNCT) was investigated. MC codes MCNP and GEANT4 were compared. MCNP was chosen for neutron capture reaction calculations. Gd neutron capture reaction includes both very short range (Auger electrons) and long range (IC electrons and gamma) products. In GdNCB the high-energetic gamma gives an almost flat absorbed dose delivery pattern, up to 4 mm around the stent. Dose distribution at the edges and inside the stent may prevent stent edge and in-stent restenosis. For GdNCT the absorbed dose from prompt gamma will dominate over the dose from IC and Auger electrons in an in vivo situation. The absorbed dose from IC electrons will enhance the total absorbed dose in the tumours and contribute to the cell killing. In paper IV a model for calculation of inter-cluster cross-fire radiation dose from β-emitting radionuclides in a breast cancer model was developed. GEANT4 was used for obtaining absorbed dose. The dose internally in cells binding the isotope (self-dose) increased with decreasing β-energy except for the radionuclides with substantial amounts of conversion electrons and Auger electrons. An effective therapy approach may be a combination of radionuclides where the high self-dose from nuclides with low β-energy should be combined with the inter-cell cluster cross-fire dose from high energy β-particles. In paper V MC simulations using correlated sampling together with importance sampling were used to calculate spectra perturbations in detector volumes caused by the detector silicon chip and its encapsulation. Penelope and EGSnrc were used and yielded similar results. The low energy part of the electron spectrum increased but to a less extent if the silicon detector was encapsulated in low z-materials.

Radioactive seed implant brachytherapy is a common radiotherapy treatment method for prostate cancer. In current clinical practice, a seed consists of a single isotope, such as 125I or 103Pd. A seed containing a mixture of two isotopes has been proposed for prostate cancer treatment. This study investigates a method for defining a prescription dose for new seed compositions based on matching the biological equivalent dose (BED) of a reference plan. Ten prostate cancer cases previously treated using single isotope seeds (5 using 125I seeds and 5 using 103Pd seeds) were selected for this study. Verification of the method was done by calculating prescription doses for 103Pd and 125I seeds. A prescription dose for a 50/50 hybrid seed was calculated. Number and location of seeds remained invariant within each case. The BED distributions for hybrid and single isotope seed plans were generated and matched to the BED distribution generated off of the optimized plans. For the 125I isotopes, the dose necessary to cover 90% of the prostate with a BED of 110 Gy is 145 Gy. For the same BED coverage, the dose for 103Pd and 50/50 hybrid seed is 120 Gy and 137 Gy respectively. A method is introduced for obtaining prescription doses for new brachytherapy sources. The method was verified by obtaining doses for 125I and 103Pd isotopes which match clinical prescription doses. The method developed is robust enough to calculate prescription doses in any region of interest, for any seed type, and for any isotope as long as the BED coverage remains invariant with respect to the treatment plan. Numerical calculations were performed to derive analytical conversions of total dose to BED for 50/50, 75/25 and 25/75 hybrid seeds. These analytical conversions are faster than the original numerical methods employed allowing for real-time BED optimization for hybrid seeds. Varying seed distribution was seen not to influence the analytical conversions. It was observed that when total dose remained invariant while individual isotope contributions varied, the value of BED varied. The BED variance was seen to be the smaller at larger BED values (~2% at 100 Gy). Using the conversions derived in this paper, BED based optimization for hybrid seeds are now performable. However, these conversions should only be used in high dose regions due to high uncertainty in the low regime.

Διευρεύνηση της μεθόδου του ακτινοεμβολισμού με μικροσφαιρίδια Υ-90 για τη αντιμετώπιση ηπατικών όγκων. Βελτίωση της image-based δοσιμετρίας προτείνοντας PET ιχνηθέτες. / Investigation of the method of radioembolization with Y90 microspheres for the treatment of liver malignancies. Improvement of the image-based dosimetry proposing the use of PET tracers.