Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 6 uppsatser.

O 68Ga é um radionuclídeo promissor para a medicina nuclear, decaindo por emissão de pósitrons com abundância de 89%, apresentando tempo de meia vida física de 68 minutos, o que é compatível com a farmacocinética de muitas biomoléculas e substratos de baixo peso molecular. Outra característica importante é a sua disponibilidade por um sistema de gerador, onde o radionuclídeo pai, 68Ge (t1/2 = 270,95 dias) é adsorvido em uma coluna e o filho, 68Ga, é eluído na forma iônica 68Ga3+. O desenvolvimento dos geradores de 68Ge/68Ga teve início na década dos anos 60, mas o seu uso clínico começou a ser aceitável e relevante apenas recentemente. O método de separação do 68Ge do 68Ga mais utilizado é o sistema cromatográfico de troca iônica, devido sua praticidade de operação, mas outros sistemas de geradores já foram propostos, como de extração por solvente e técnica de evaporação. Atualmente, os geradores de 68Ge/68Ga são disponíveis comercialmente tanto com colunas utilizando matrizes inorgânicas preparadas com TiO2 ou SnO2 como também usando resina orgânica. A eficiência de eluição do 68Ga varia de 70 % a 80 %, apresentando uma queda ao longo do tempo. Os níveis de contaminação do 68Ge vão de 10-2 a 10-3 %, porém ocorre um aumento nos níveis de contaminação após longos períodos de uso. Mesmo com todos os avanços tecnológicos, ocorridos nas últimas décadas, no desenvolvimento dos geradores de 68Ge/68Ga, o eluato de 68Ga dos geradores comerciais ainda não é adequado para uso direto em seres humanos e algumas melhorias nos sistemas precisam ser feitas para diminuir os níveis de contaminação de 68Ge e impurezas químicas. O objetivo principal deste trabalho foi desenvolver um sistema de gerador de 68Ge/68Ga com o qual se pudesse eluir o 68Ga com qualidade necessária para uso clínico. O comportamento químico do Ge e do Ga foi avaliado em vários materiais adsorvedores inorgânicos. Foram desenvolvidos dois tipos de sistemas de geradores de 68Ge/68Ga utilizando o TiO2 como material adsorvedor: sistema de eluição com pressão manual e sistema de eluição a vácuo, controlado. As eficiências dos geradores foram similares às encontradas nos geradores comerciais, assim como os níveis de impurezas no eluato. Um novo método para o controle radionuclídico foi desenvolvido e apresentou resultados satisfatórios para determinação da contaminação do 68Ge no eluato do gerador. Foi proposto um protótipo de gerador capaz de fornecer 68Ga com a qualidade necessária para ser utilizado em aplicações médicas. / The 68Ga is a promising radionuclide for nuclear medicine, decaying by positron emission with an abundance of 89%, with physical half-life of 68 minutes, which is compatible with the pharmacokinetics of many biomolecules and low molecular weight substrates. Another important feature is its availability through a generator system, where the parent radionuclide, 68Ge (t1/2 = 270.95 days) is adsorbed on a column and the daughter, 68Ga, is eluted in an ionic form 68Ga3+. The development of 68Ge/68Ga generators began in the 60s, but its clinical use began to be acceptable and relevant only recently. The method of separation of 68Ge and 68Ga most used is the ion-exchange chromatographic system, due to its practical operation, but other generator systems have been proposed, such as solvent extraction and evaporation technique. Currently, 68Ge/68Ga generators are commercially available using inorganic matrices columns prepared with TiO2 or SnO2 as well using organic resin. The efficiency of 68Ga elution ranges from 70% to 80%, decreasing over time. The 68Ge breakthrough varies from 10-2 to10-3 % or lower in a fresh generator, but there is an increase in the levels of contamination after long periods of use. Even with all the technological advances in the development of 68Ge/68Ga generators in the past decades, the 68Ga eluted from commercial generators is not suitable for direct use in humans and some improvements in the systems need to be made to reduce the 68Ge breakthrough and chemical impurities levels. The main objective of this work was to develop a 68Ge/68Ga generator system is which 68Ga could be eluted with quality required for clinical use. The chemical behavior of Ge and Ga was evaluated on various inorganic adsorbents materials. Two types of 68Ge/68Ga generator systems were developed using TiO2 as adsorbent material: elution system with manual pressure and vacuum controlled. The efficiencies of the generators were similar to those found in commercial generators, as well as the impurity levels in the eluate. A new method for radionuclidic control was developed and showed good results for the determination of 68Ge breakthrough in 68Ga eluate. It was proposed a prototype 68Ga generator capable of providing the quality needed for use in medical applications.

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Orientador: Sonia Marta Moriguchi / Resumo: O câncer de mama é o tipo mais comum entre as mulheres no Brasil e no mundo, com 28% de novos casos a cada ano. O diagnóstico tardio pode identificar carcinoma de mama localmente avançado (CMLA) que necessita tratamento sistêmico quimioterápico pré-operatório que visam reduzir o tamanho do tumor e da carga tumoral. A quimiorresistência pode estar relacionada à expressão de glicoproteína P (GpP), que promove o efluxo celular da droga, diminuindo o tempo de permanência da droga na célula e, consequentemente a apoptose celular. O sestamibi-99mTc utilizado na realização da cintilografia de mamas (CM) é um substrato dessas proteínas, similar às drogas quimioterápicas, sendo o único método de imagem a representar o tempo de permanência dessa droga. O índice preditor da resposta quimioterápica por cintilografia tem sido utilizado para prever o tempo de permanência dessas drogas nessas células. O objetivo desse estudo foi verificar se o índice preditor de resposta quimioterápica neoadjuvante obtido por cintilografia de mamas com sestamibi-99mTc proposto por Alonso e cols. relacionou-se com resposta quimioterápica do estudo anatomopatológico da mama pós-cirurgia (AP), considerado padrão ouro, analisando-se os índices isolados: índice precoce (IP) e índice tardio (IT) e associados (IP+IT). Tratou-se de estudo transversal, observacional e descritivo, com coleta retrospectiva de dados de prontuários de portadores de CMLA atendidas nessa Instituição no período de 2012-2017, que foram subm... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Breast cancer is the most common cancer among women, both in Brazil and globally, with 28% of cases each year being new. Delayed diagnosis can identify locally advanced breast carcinoma (LABC), which requires preoperative systemic chemotherapy that aims to reduce the size and load of the tumor. The chemo-resistance may be related to expression of glycoprotein P (GpP) that promotes cellular efflux of the drug, diminishing not only its time within the cell but consequently cellular apoptosis. Sestamibi99mTc, utilized in performing scintimammography (SMM), is a substrate of these proteins, similar to chemotherapeutic drugs, being the only imaging method to represent the permanence time of this drug. The predictive index of chemotherapeutic response by SMM has been utilized to predict the permanence time of chemotherapeutic drugs into these cells. This study aimed to verify whether the predictive index of neoadjuvant chemotherapeutic response, obtained by SMM with sestamibi99mTc proposed by Alonso and colleagues, is related to the chemotherapeutic response, as shown by postoperative anatomopathological study of the breasts (AP), considered the gold standard, analyzing the isolated indices, early index (EI) and late index (LI), and associated index (EI+LI). This was a transversal, observational and descriptive study, with retrospective data collected from charts of patients who were carriers of LABC attended at this Institution in the period from 2012 to 2017, that were submitted ... (Complete abstract click electronic access below) / Mestre

This thesis deals with analysis and evaluation of risks associated with the release of radioactive materials during the transport, eventual accidents and radiation load handling throughout the all transport chain to nuclear medicine workplace in relation to current legislation and technical support for the transported substances. The theoretical part is focused on describing the current state of these issues, the reasons for using the radionuclides in the Czech Republic, their transport and description of legislation associated with that all. The research part shows the analysis of the health risks of people who might come in contact with the release of radioactivity. Then the analysis solves such consequences. In this work we mapped out the production and use of artificial radionuclides, modes of transportation and its technical security and handling of radionuclides during the transport. We also present the research in some possible accident during the transport. As well as emergency readiness and procedures of the Integrated Rescue System. In discussion there are throughout the commentary compared the following: determined state laws transport safety, radiation burden and risks of transports. In conclusion we found out that the level of legislation and the radiation burden is at an acceptable level. The work comes with its own proposal for improving transportation safety of radionuclides in the Czech Republic and that is to introduce the rights-of-way to vehicles described above.

Possible risks of using radioactive materials are a highly discussed topic nowadays. This work is dealing with this problem and it is focused on possible risks of using radioactive materials from the ex-treatment plant of uranium ores MAPE Mydlovary. In introductory chapters I am describing the current state of ex-treatment plant of uranium ores. I am dealing with the history of operation of MAPE, information about sludge lagoons and about stored sediments in them and other characteristics concerning this operation. For years, sediments in which radionuclides are contained have been stored in treatment plants and that is why I am dealing with ionizing radiation. Because the topic is the using of radioactive materials which can be used mainly by terrorists, I am also describing this worldwide phenomenon of recent years where I first of all focused on super-terrorism using radioactive weapons, namely so-called ?dirty bombs?. The target of this work is to find out possibilities of using radioactive materials from the ex-treatment plant. Therefore I measured values of radioactivity and exposition of radiation at some places with the help of exploratory research. That meant sampling of soils and water and also measurement of power of dose equivalent of radiation gamma. After gathering information of needed radiation values I carried out simulation of possible using of radioactive materials from the premises MAPE. By means of dirty bomb I used the programme TerEx at using radioactive material. Then I carried out several calculations which were focused on inhalation, ingestion or outdoor radiation from radioactive materials and also calculation how much it is necessary to gain a significant source of ionizing radiation. From these sources I have deduced impacts for individuals, society or environment. Based on analysis and evaluation of given problems, my set hypothesis ?By using radioactive materials from the ex-treatment plant of uranium ores MAPE Mydlovary a serious threat to people will not occur? was confirmed. Results of my work can be used as a study material for completing and broadening knowledge about risks resulting from using radioactive materials. Further an increase of foreknowledge and explanation of certain consequences of ionizing radiation on humans from materials from the ex-treatment plant of uranium ores MAPE Mydlovary, for inhabitants of Mydlovary and surrounding areas and also useful information for lay and professional society which is interested in these problems.

The aim of my diploma thesis was to assess possibilities of tracing and, consequently, identifying radionuclides in transported materials detected by detection frames on the protected area border of the nuclear power plant of Temelín, by means of the portable spectrometer Inspector 1000. To achieve this, I designed a series of measurements based on a simulated passage of a motor vehicle fitted with ionizining radiation sources of various activities at the designed points of measurement so that these measurements corresponded as close as possible to the actual passage of vehicles with large-sized loads. Recorded values were analysed and marginal activities for the particular measuring points were fixed. Computation correctness was then verified by another passage of the vehicle through the measuring device. Specified values of the marginal activities at the particular measuring points were, for comparison, consequently measured by the portable spectrometer Inspector 1000. Measurement results proved that the portable spectrometer Inspector 1000 can efficiently detect, identify and locate the sources of ionizing radiation causing the alarm level to be exceeded on a stable measuring device at the fixed measuring points, with a higher sensitivity than a stable measuring device. Conclusions of this diploma thesis will be given to the radiation protection unit of the nuclear power plant of Temelín as a basis for specification or even expansion of the methods of measuring ionizining radiation sources when transporting large-sized loads in the nuclear power plant, and their introduction into the monitoring programme.

O câncer de próstata é considerado o segundo mais comum na população masculina em todo o mundo e ocupa a 15ª posição em mortes por câncer, em homens, representando cerca de 6% do total de mortes por câncer no mundo. O antígeno de membrana prostático específico (PSMA) é uma glicoproteína tipo II transmembrânica superexpressa no câncer de próstata, suas metástases e em neovascularizações relacionadas a tumores sólidos, que tem estimulado o desenvolvimento de pequenas moléculas inibidoras do receptor de PSMA, que carreguem agentes terapêuticos. Este trabalho pretendeu estudar de forma inédita a marcação e estabilidade radioquímica do Glu-NH-CO-NH-Lys(Ahx)-DOTA com 177Lu (PSMA-DOTA-177Lu) e avaliar seu potencial para a terapia do câncer de próstata. O radiofármaco foi obtido com pureza radioquímica elevada (PR > 95%) em todas as condições estudadas e permaneceu inalterada em ≤ - 20 °C até 48 horas, mesmo em atividade específica alta (74 MBq/μg). O ensaio de ligação específica do PSMADOTA- 177Lu mostrou que a fração do peptídeo que se ligou às células LNCaP de tumor de próstata foi de 1,79 ± 0,21 %, 2,47 ± 0,03 %, 3,07 ± 0,01 % e 4,13 ± 0,27%, para as concentrações de 0,15 x 106, 0,3 x 106, 0,5 x 106 e 1 x 106 células, respectivamente. O ensaio de internalização do PSMA-DOTA-177Lu sugere que o maior percentual da ligação específica do radiofármaco às células LNCaP corresponde à fração da ligação de superfície (99,03 ± 0,84 %). Os parâmetros farmacocinéticos determinados no estudo in vivo em camundongos Balb/c são compatíveis com o rápido clareamento sanguíneo e excreção renal, além de apresentar apreciável captação tumoral in vivo (2,76 ± 1,21 % Al/g) após 4 horas de administração do radiofármaco. Os estudos em estabilidade em soro humano demonstram estabilidade alta do radiofármaco PSMA-DOTA-177Lu por um período de até 24 horas, que foi confirmada pela baixa captação óssea demonstrada nos estudos in vivo de biodistribuição. O estudo de variação da atividade possibilitou estabelecer a atividade específica ideal (MBq/μg), que será extrapolada para um piloto de produção do radiofármaco. Os resultados favoráveis deste estudo encorajam a perspectiva de realização de ensaio clínico controlado deste novo radiofármaco, avaliando seu potencial para aplicação no tratamento do câncer de próstata. / Prostate cancer is the second most frequently worldwide diagnosed cancer among males and ranks the 15th common cause of death from cancer in men, comprising 6% of the world\'s total cancer deaths. The prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein, which is overexpressed in prostate cancer as well as in the neovasculature of solid tumors and metastasis. These features render PSMA an ideal target for developing small molecules inhibitors of PSMA and therapeutic approaches to targeted drugs delivery. This work intended to study in an unprecedented way the radiochemical labeling and stability of Glu-NHCO- NH-Lys (Ahx)-DOTA with 177Lu (177Lu-PSMA-DOTA) and its potential anti-tumor effects in prostate cancer. The radiopharmaceutical PSMA-177Lu was obtained with high radiochemical purity (RP > 95%) under all studied conditions and remained unchanged up to 48 hours (high at ≤ -20 °C), even at high specific activity (74 MBq / μg). The cellular uptake of PSMA-DOTA-177Lu was determined using PSMAexpressing LNCaP cells and showed a binding of 1.79 ± 0.21%, 2.47 ± 0.03%, 3.07 ± 0.01% and 4.13 ± 0.27%, to 0.15 × 106, 0.3 × 106, 0.5 × 106 and 1 × 106 LNCaP cells, respectively. The PSMA-DOTA-177Lu internalization assay revealed that the membrane-bound activity (non-internalized peptide) to LNCap cells, was 99.03 ± 0.84%. Moreover, the pharmacokinetic in vivo studies performed in Scid mice resulted in a rapid blood clearance and renal excretion, and showed significant tumor uptake (2.76 ± 1.21% lA/g) 4 hours after PSMA-DOTA-177Lu administration. Stability studies in human serum demonstrated high PSMA-DOTA-177Lu stability over 24 hours, which is in agreement with the low bone uptake obtained in the in vivo biodistribution studies. Furthermore, the comparative study aiming to establish the ideal PSMA-DOTA-177Lu specific activity (MBq / μg) will be considered for further radiopharmaceutical production. The pre-clinical data obtained from this study suggested a great potential for PSMA-DOTA-177Lu to be included in clinical trials and to make a major contribution to the treatment of prostate cancer.