No presente trabalho, foram padronizados os radionuclídeos emissores beta puros 32P e 90Sr 90Y. O primeiro foi medido nos sistemas comerciais de cintilação líquida TRICARB 2100 e HIDEX 300SL, que utilizam, respectivamente, dois e três tubos fotomultiplicadores. A análise dos dados adquiridos pelo primeiro e segundo sistemas foi realizada pela aplicação dos métodos CIEMAT/NIST e TDCR, respectivamente. Para padronização da solução de 32P, foi também utilizado o sistema 4πβ empregando-se a técnica de autoabsorção. A solução de 90Sr 90Y foi padronizada no sistema de cintilação líquida, HIDEX 300SL, pelo método TDCR, e pela técnica do traçador, no sistema de coincidência 4πβ-γ o qual é composto por um contador proporcional à gás fluente, acoplado a dois cristais cintiladores de NaI(Tl). A taxa de desintegração foi determinada pela técnica de extrapolação, por meio de absorvedores externos. Para aplicação da técnica do traçador, foi utilizada uma solução de 60Co, emissor beta-gama previamente padronizado no sistema de coincidências. Foi realizada, também, uma simulação dos processos de detecção neste sistema por meio do programa ESQUEMA, que, pela simulação de Monte Carlo, prediz a curva de extrapolação da eficiência. Os resultados obtidos para o 32P nos sistemas utilizados apresentaram um bom acordo, dentro das incertezas experimentais, bem como os obtidos para o 90Sr 90Y, em sistema de cintilação e sistema de coincidência, apresentando bom acordo, dentro das incertezas experimentais. O resultado obtido pela técnica de Monte Carlo apresentou boa concordância com o valor obtido com o sistema de coincidência. Os resultados indicam a qualidade e boa precisão dos sistemas de detecção utilizados neste trabalho, quando empregados para fins metrológicos. / In the present work, pure beta emitters radionuclides 32P and 90Sr - 90Y were standardized. The first one was measured in commercial liquid scintillation systems TRICARB 2100 and HIDEX 300SL, which use, respectively, two and three photomultiplier tubes. The analysis of the data acquired by the first and second systems was performed using the CIEMAT / NIST and TDCR methods, respectively. For standardization of the 32P solution, the 4πβ system was also used, using the self-absorption technique. The 90Sr - 90Y solution was standardized in the liquid scintillation system, HIDEX 300SL, by the TDCR method, and by the tracer technique, in the coincidence system 4πβ-γ which is composed by a proportional counter to the flowing gas, coupled to two NaI(Tl) scintillation crystals. The rate of disintegration was determined by the extrapolation technique, by means of external absorbers. For the application of the tracer technique, a 60Co solution, a beta-gamma emitter previously standardized in the coincidence system, was used. It was also performed a simulation of the detection processes in this system through the program ESQUEMA, which, by Monte Carlo simulation, predicts the efficiency extrapolation curve. The results obtained for the 32P in the systems used presented a good agreement, within the experimental uncertainties, as well as those obtained for the 90Sr - 90Y, in scintillation system and coincidence system, showing good agreement, within the experimental uncertainties. The result obtained by the Monte Carlo technique showed good agreement with the value obtained with the coincidence system. The results indicate the quality and good accuracy of the detection systems used in this work, when used for metrological purposes.

No presente trabalho, foram padronizados os radionuclídeos emissores beta puros 32P e 90Sr 90Y. O primeiro foi medido nos sistemas comerciais de cintilação líquida TRICARB 2100 e HIDEX 300SL, que utilizam, respectivamente, dois e três tubos fotomultiplicadores. A análise dos dados adquiridos pelo primeiro e segundo sistemas foi realizada pela aplicação dos métodos CIEMAT/NIST e TDCR, respectivamente. Para padronização da solução de 32P, foi também utilizado o sistema 4πβ empregando-se a técnica de autoabsorção. A solução de 90Sr 90Y foi padronizada no sistema de cintilação líquida, HIDEX 300SL, pelo método TDCR, e pela técnica do traçador, no sistema de coincidência 4πβ-γ o qual é composto por um contador proporcional à gás fluente, acoplado a dois cristais cintiladores de NaI(Tl). A taxa de desintegração foi determinada pela técnica de extrapolação, por meio de absorvedores externos. Para aplicação da técnica do traçador, foi utilizada uma solução de 60Co, emissor beta-gama previamente padronizado no sistema de coincidências. Foi realizada, também, uma simulação dos processos de detecção neste sistema por meio do programa ESQUEMA, que, pela simulação de Monte Carlo, prediz a curva de extrapolação da eficiência. Os resultados obtidos para o 32P nos sistemas utilizados apresentaram um bom acordo, dentro das incertezas experimentais, bem como os obtidos para o 90Sr 90Y, em sistema de cintilação e sistema de coincidência, apresentando bom acordo, dentro das incertezas experimentais. O resultado obtido pela técnica de Monte Carlo apresentou boa concordância com o valor obtido com o sistema de coincidência. Os resultados indicam a qualidade e boa precisão dos sistemas de detecção utilizados neste trabalho, quando empregados para fins metrológicos. / In the present work, pure beta emitters radionuclides 32P and 90Sr - 90Y were standardized. The first one was measured in commercial liquid scintillation systems TRICARB 2100 and HIDEX 300SL, which use, respectively, two and three photomultiplier tubes. The analysis of the data acquired by the first and second systems was performed using the CIEMAT / NIST and TDCR methods, respectively. For standardization of the 32P solution, the 4πβ system was also used, using the self-absorption technique. The 90Sr - 90Y solution was standardized in the liquid scintillation system, HIDEX 300SL, by the TDCR method, and by the tracer technique, in the coincidence system 4πβ-γ which is composed by a proportional counter to the flowing gas, coupled to two NaI(Tl) scintillation crystals. The rate of disintegration was determined by the extrapolation technique, by means of external absorbers. For the application of the tracer technique, a 60Co solution, a beta-gamma emitter previously standardized in the coincidence system, was used. It was also performed a simulation of the detection processes in this system through the program ESQUEMA, which, by Monte Carlo simulation, predicts the efficiency extrapolation curve. The results obtained for the 32P in the systems used presented a good agreement, within the experimental uncertainties, as well as those obtained for the 90Sr - 90Y, in scintillation system and coincidence system, showing good agreement, within the experimental uncertainties. The result obtained by the Monte Carlo technique showed good agreement with the value obtained with the coincidence system. The results indicate the quality and good accuracy of the detection systems used in this work, when used for metrological purposes.

In this thesis, manufacturing of microirradiators, electrodeposition of radioactive elements such as Ni-63, and applications of these radioactive sources are discussed. Ni-63 has a half life of 100 years and a low energy beta electron of 67 keV, ideal for low dose low linear energy transfer (LET) research. The main focus of the research is on the novel Ni-63 microirradiator. It contains a small amount of total activity of radiation but a large flux, allowing the user to safely handle the microirradiator without extensive shielding. This thesis is divided into nine chapters. Properties of microirradiators and various competing radioactive sources are compared in the introduction (chapter 1). Detailed description of manufacturing Ni-63 microirradiator using the microelectrode as the starting point is outlined in chapter 2. The microelectrode is a 25 µm in diameter Pt disk sealed in a pulled 1 mm diameter borosilicate capillary tube, as a protruding wire or recessed disk microelectrode. The electrochemically active surface area of each is verified by cyclic voltammetry. Electrodeposition of nickel with a detailed description of formulation of the electrochemical bath in a cold "non-radioactive setting" was optimized by using parameters as defined by pourbaix diagrams, radioactive electroplating of Ni-63, and incorporation of safety regulations into electrodeposition. Calibration and characterization of the Ni-63 microirradiators as protruding wire and recessed disk microirradiators is presented in chapter 3. In chapters 4 through 6, applications of the Ni-63 microirradiators and wire sources are presented. Chapter 4 provides a radiobiological application of the recessed disk microirradiator and a modified flush microirradiator with osteosarcoma cancer cells. Cells were irradiated with 2000 to 1 Bq, and real time observations of DNA double strand breaks were observed. A novel benchtop detection system for the microirradiators is presented in chapter 5. Ni-63 is most commonly measured by liquid scintillation counters, which are expensive and not easily accessible within a benchtop setting. Results show liquid scintillation measurements overestimates the amount of radiation coming from the recessed disk. A novel 10 µCi Ni-63 electrochemically deposited wire acting as an ambient chemical ionization source for pharmaceutical tablets in mass spectrometry is in chapter 6. Typically, larger radioactive sources (15 mCi) of Ni-63 have been used in an ambient ionization scenario. Additionally, this is the first application of using Ni-63 to ionize in atmosphere pharmaceutical tablets, leading to a possible field portable device. In the last chapters, chapters 7 through 8, previous microirradiator experiments and future work are summarized. Chapter 7 illustrates the prototype of the electrochemically deposited microirradiator, the Te-125 microirradiator. In conjunction with Oak Ridge National Laboratory, Te-125m is a low dose x-ray emitting element determined to be the best first prototype of an electrochemically deposited microirradiator. Manufacturing, characterization, and experiments that were not successful leading to the development of the Ni-63 microirradiator are discussed. In chapter 8, future work is entailed in continuing on with this thesis project. The work presented in the thesis is concluded in chapter 9.

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京都大学 / 新制・論文博士 / 博士(工学) / 乙第13545号 / 論工博第4208号 / 新制||工||1984(附属図書館) / (主査)教授 米田 稔, 教授 松井 康人, 准教授 福谷 哲 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

90Y (T1/2 = 2,67 dias; Eβmáx = 2,28 MeV) é um radionuclídeo com eficácia estabelecida para diversas terapias de câncer, marcando biomoléculas e no tratamento da radiosinovectomia. Devido às suas propriedades nucleares, é obtido através do decaimento do 90Sr (T1/2 = 28 anos), na forma de um gerador. Vários tipos de geradores de 90Sr/90Y foram desenvolvidos, e os mais empregados são os que usam resinas de troca catiônica, onde Sr e Y são adsorvidos e 90Y é seletivamente eluído com acetato ou EDTA. A desvantagem deste tipo de gerador é a radiólise, que degrada o seu uso. O gerador eletroquímico é uma solução proposta devido ao fato de não haver efeitos significativos da radiação sobre o próprio gerador. Neste conceito, a diferença entre os potenciais eletroquímicos dos elementos Y e Sr é utilizada para se obter uma rápida separação do 90Y do 90Sr. A produção de 90Y via formação de colóides é o método mais simples para a separação, baseando-se na formação de colóides de Y em pH altamente alcalino, podendo ser filtrado e separado do Sr, sendo posteriormente dissolvido em HCl. O objetivo deste trabalho consistiu no desenvolvimento de tecnologias para o preparo de geradores de 90Sr/90Y, onde foram desenvolvidos três tecnologias, a saber: geradores do tipo coluna utilizando resinas catiônicas, geradores via formação de colóides e geradores eletroquímicos. Foram também avaliadas metodologias para o controle de qualidade radionuclídico do 90Y dos geradores desenvolvidos: cintilação líquida, identidade radionuclídica, cromatografia por extração em papel (EPC) utilizando complexantes para 90Y e técnica por Espectrometria de Emissão Ótica com Plasma Indutivamente Acoplado (ICPOES). Os resultados mostraram que os geradores utilizando resinas catiônicas obtiveram os melhores resultados em relação ao rendimento e eficiência (~ 83%) de eluição, reprodutibilidade e a pureza radionuclídica. O gerador eletroquímico mostrou um potencial para o desenvolvimento, tendo a vantagem de não sofrer os efeitos da radiólise do par 90Sr/90Y, como acontece com a resina. Das metodologias de controle qualidade radionuclídica estudadas, uma comparação e avaliação mostrou que a EPC é muito sensível e permite a avaliação praticamente instantânea da qualidade do 90Y eluído dos geradores. / 90Y (T1/2 = 2,67 d; Eβmáx = 2,28 MeV) is a radionuclide with efficacy established for various cancer therapies, labeling biomolecules and treating of radiosinovectomy. Due to its nuclear properties, is obtained through the decay of 90Sr T1/2 = 28 y in the form of a generator. Several types of 90Sr/90Y generators were developed, and the most employed are the cation exchange resins, where Sr and Y are adsorbed and 90Y is selectively eluted with acetate or EDTA. The disadvantage of this type of generator is the radiolysis, which degrades its use. The electrochemical generator is a proposed solution because there is no significant effect of radiation. In this concept, the difference between the electrochemical potentials of the elements Sr and Y is used to obtain a rapid separation of 90Y from 90Sr. The production of 90Y via colloid formation is the simplest method for the separation, based on the colloid formation of Y in high alkaline pH, which can be filtered and separated from Sr, and subsequently dissolved in HCl. The objective of this work was the development of technologies for the preparation of 90Sr/90Y generators, and three technologies were developed: generators using cation resins columns, generators through colloid formation and electrochemical generators. Radionuclidic quality control of 90Y was also evaluated by liquid scintillation, radionuclide identity, extraction paper chromatography (EPC) using complexing agents for 90Y and by Optical Emission Spectrometry with Inductively Coupled Plasma (ICP-OES). The results showed that generators using cation resins have the best results related to the elution efficiency (~83%), the reproducibility and radionuclidic purity. The electrochemical generator showed a potential for development, having the advantage of not suffering the effects of radiolysis of the pair 90Sr/90Y as the resin. A comparison and evaluation of the methods of the radionuclidic quality control showed that the EPC is very sensitive and allows for virtually instantaneous assessment of the quality of 90Y generator.

90Y (T1/2 = 2,67 dias; Eβmáx = 2,28 MeV) é um radionuclídeo com eficácia estabelecida para diversas terapias de câncer, marcando biomoléculas e no tratamento da radiosinovectomia. Devido às suas propriedades nucleares, é obtido através do decaimento do 90Sr (T1/2 = 28 anos), na forma de um gerador. Vários tipos de geradores de 90Sr/90Y foram desenvolvidos, e os mais empregados são os que usam resinas de troca catiônica, onde Sr e Y são adsorvidos e 90Y é seletivamente eluído com acetato ou EDTA. A desvantagem deste tipo de gerador é a radiólise, que degrada o seu uso. O gerador eletroquímico é uma solução proposta devido ao fato de não haver efeitos significativos da radiação sobre o próprio gerador. Neste conceito, a diferença entre os potenciais eletroquímicos dos elementos Y e Sr é utilizada para se obter uma rápida separação do 90Y do 90Sr. A produção de 90Y via formação de colóides é o método mais simples para a separação, baseando-se na formação de colóides de Y em pH altamente alcalino, podendo ser filtrado e separado do Sr, sendo posteriormente dissolvido em HCl. O objetivo deste trabalho consistiu no desenvolvimento de tecnologias para o preparo de geradores de 90Sr/90Y, onde foram desenvolvidos três tecnologias, a saber: geradores do tipo coluna utilizando resinas catiônicas, geradores via formação de colóides e geradores eletroquímicos. Foram também avaliadas metodologias para o controle de qualidade radionuclídico do 90Y dos geradores desenvolvidos: cintilação líquida, identidade radionuclídica, cromatografia por extração em papel (EPC) utilizando complexantes para 90Y e técnica por Espectrometria de Emissão Ótica com Plasma Indutivamente Acoplado (ICPOES). Os resultados mostraram que os geradores utilizando resinas catiônicas obtiveram os melhores resultados em relação ao rendimento e eficiência (~ 83%) de eluição, reprodutibilidade e a pureza radionuclídica. O gerador eletroquímico mostrou um potencial para o desenvolvimento, tendo a vantagem de não sofrer os efeitos da radiólise do par 90Sr/90Y, como acontece com a resina. Das metodologias de controle qualidade radionuclídica estudadas, uma comparação e avaliação mostrou que a EPC é muito sensível e permite a avaliação praticamente instantânea da qualidade do 90Y eluído dos geradores. / 90Y (T1/2 = 2,67 d; Eβmáx = 2,28 MeV) is a radionuclide with efficacy established for various cancer therapies, labeling biomolecules and treating of radiosinovectomy. Due to its nuclear properties, is obtained through the decay of 90Sr T1/2 = 28 y in the form of a generator. Several types of 90Sr/90Y generators were developed, and the most employed are the cation exchange resins, where Sr and Y are adsorbed and 90Y is selectively eluted with acetate or EDTA. The disadvantage of this type of generator is the radiolysis, which degrades its use. The electrochemical generator is a proposed solution because there is no significant effect of radiation. In this concept, the difference between the electrochemical potentials of the elements Sr and Y is used to obtain a rapid separation of 90Y from 90Sr. The production of 90Y via colloid formation is the simplest method for the separation, based on the colloid formation of Y in high alkaline pH, which can be filtered and separated from Sr, and subsequently dissolved in HCl. The objective of this work was the development of technologies for the preparation of 90Sr/90Y generators, and three technologies were developed: generators using cation resins columns, generators through colloid formation and electrochemical generators. Radionuclidic quality control of 90Y was also evaluated by liquid scintillation, radionuclide identity, extraction paper chromatography (EPC) using complexing agents for 90Y and by Optical Emission Spectrometry with Inductively Coupled Plasma (ICP-OES). The results showed that generators using cation resins have the best results related to the elution efficiency (~83%), the reproducibility and radionuclidic purity. The electrochemical generator showed a potential for development, having the advantage of not suffering the effects of radiolysis of the pair 90Sr/90Y as the resin. A comparison and evaluation of the methods of the radionuclidic quality control showed that the EPC is very sensitive and allows for virtually instantaneous assessment of the quality of 90Y generator.

Improving the functionality and reducing revision rates are important driving forces in the development of orthopaedic implants. FibMat is a fibrinogen based matrix developed towards commercialisation by the company Optovent AB. This matrix can be coated on implants and act as a local drug delivery system for bisphosphonates (BPs). BPs are drugs inhibiting bone resorption, and applied with FibMat to improve stability of implants in bone, e.g. when fixing bone fractures. In this thesis, FibMat loaded with BP (FibMat/BP) was coated on stainless-steel screws and titanium screws in order to investigate some technology properties relevant to its clinical applicability. Bone-mimicking materials were used to study scrape-off effect upon insertion. The coagulation properties of fibrinogen as well as the structural properties of BPs were studied after exposure to gamma radiation. The screws were coated with FibMat and BP (alendronate and 14C-alendronate) using standard coupling techniques. The total amount and distribution of BP after insertion was measured by liquid scintillation and autoradiography. Coagulation assays were performed in order to determine the coagulation properties of fibrinogen, exposed to doses up to 35 kGy, mixed with thrombin. The structural properties of four different BPs (alendronate, pamidronate, zoledronate and ibandronate), exposed to doses up to 35 kGy were analysed by transmission infrared spectroscopy. The results show that FibMat/BP coating on porous stainless-steel screws is virtually unaffected by insertion into bone materials. The anodised, planar titanium screws are more affected by the insertion process, but an even BP distribution in the cancellous material is indicated. The coagulation assays show that gamma-irradiated fibrinogen has a slower coagulation process compared to non-irradiated fibrinogen and form interrupted network unable to clot. The chemical structures of the BPs seem unaffected by exposure to gamma irradiation. In conclusion, the FibMat/BP is a promising technology for local distribution of BP in conjunction with bone implants.

<p>Improving the functionality and reducing revision rates are important driving forces in the development of orthopaedic implants. FibMat is a fibrinogen based matrix developed towards commercialisation by the company Optovent AB. This matrix can be coated on implants and act as a local drug delivery system for bisphosphonates (BPs). BPs are drugs inhibiting bone resorption, and applied with FibMat to improve stability of implants in bone, e.g. when fixing bone fractures. In this thesis, FibMat loaded with BP (FibMat/BP) was coated on stainless-steel screws and titanium screws in order to investigate some technology properties relevant to its clinical applicability. Bone-mimicking materials were used to study scrape-off effect upon insertion. The coagulation properties of fibrinogen as well as the structural properties of BPs were studied after exposure to gamma radiation.</p><p>The screws were coated with FibMat and BP (alendronate and 14C-alendronate) using standard coupling techniques. The total amount and distribution of BP after insertion was measured by liquid scintillation and autoradiography. Coagulation assays were performed in order to determine the coagulation properties of fibrinogen, exposed to doses up to 35 kGy, mixed with thrombin. The structural properties of four different BPs (alendronate, pamidronate, zoledronate and ibandronate), exposed to doses up to 35 kGy were analysed by transmission infrared spectroscopy.</p><p>The results show that FibMat/BP coating on porous stainless-steel screws is virtually unaffected by insertion into bone materials. The anodised, planar titanium screws are more affected by the insertion process, but an even BP distribution in the cancellous material is indicated. The coagulation assays show that gamma-irradiated fibrinogen has a slower coagulation process compared to non-irradiated fibrinogen and form interrupted network unable to clot. The chemical structures of the BPs seem unaffected by exposure to gamma irradiation. In conclusion, the FibMat/BP is a promising technology for local distribution of BP in conjunction with bone implants.</p>