CARLA DARUICH DE SOUZA

CARLA DARUICH DE SOUZA

(Fonte: Lattes)

Resumo

Bsc in Medical Physics from UNESP in Botucatu Compleated at IPEN, University of São Paulo: 1) Master's Degree: Comparison between methods for fixing iodine-125 on silver substrate for fabricating sources used in Brachytherapy / 2) PhD: Parameters for production of iodine-125 sources used in brachytherapy and "sandwich" doctorate: Washington State University - training in radiochemistry and organic chemistry / 3) Post doctorate: Production of nanosources for the treatment of cancer / 4) Project: Analysis of methods to obtain / produce nuclear material for use in a radioisotope thermoelectric generator (RTG)/ Advisor of the Professional Master's Degree in Radiation Technology in Health / Professor of the Professional Master Program in the disciplines Dosimetry for Radiotherapy and Radiotherapy Fundamentals / Professor of the Academic Master Program in the discipline TNA5805 - Brachytherapy: Fundamentals, Production, Application, Dosimetry and Quality Research Associate of KAERI - Korean Atomic Energy and Research Institute (Text obtained from the Currículo Lattes on October 6th 2021)

Formada em Física Médica pela UNESP em Botucatu Realizado no IPEN-USP/ SP: 1) Mestrado: Comparação entre métodos de fixação do iodo-125 em substrato de prata para confecção de fontes utilizadas em Braquiterapia / 2) Doutorado: Parâmetros para produção de confecção de fontes de iodo-125 utilizadas em Braquiterapia e Doutorado sanduíche: Washington State University - treinamento em radioquímica / 3) Pós doutorado: Produção de nanofontes para tratamento de câncer / 4) Projeto: Análise de formas de obtenção/produção do material nuclear para utilização em um gerador termoelétrico radioisotópico (RTG)/ Orientadora do Mestrado Profissional de Tecnologia das Radiações na Saúde/ Professora do Mestrado Profissional nas disciplinas Dosimetria para Radioterapia e Fundamentos de Radioterapia/ Professora do Mestrado Acadêmico na disciplina TNA5805 - Braquiterapia: Fundamentos, Produção, Aplicação, Dosimetria e Qualidade Research Associate do KAERI - Korean Atomic Energy and Research Institute (Texto extraído do Currículo Lattes em 06 out. 2021)

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Nationalization of brachytherapy radioactive sources in Brazil and the importance of IAEA cooperation
2023 - ROSTELATO, MARIA E.C.M.; FEHER, ANSELMO; ZEITUNI, CARLOS A.; ROSERO, WILMMER A.A.; SOUZA, CARLA D. de; MOURA, JOÃO A.
Brazil has a cancer incidence of about 625,000 cases a year. It is a public health problem, demanding constant efforts to deliver for patients the most efficient treatment modalities, improving their life expectancy and quality. Brachytherapy is a type of Radiotherapy where the radioactive source is placed close to or inside the tumor. The main advantage of the technique is to deliver the maximum dose in the target, saving healthy tissues. In Brazil, Our group had the objective of producing sources nationally, diminishing treatment costs, enabling the treatment to more patients. Some of our projects are developed in collaboration with the International Atomic Energy Agency-IAEA by technical cooperation projects. The IAEA participation is very important to provide technological transfer through scientific visits, expert missions, and contacts with more advanced centers. The financial support is also important, allowing us to buy the necessary equipment to make these cancer treatment sources production feasible in Brazil. Our team has received training through fellowships. We received some experts and organized several workshops to propagate the Brachytherapy technique at national and Latin American level. For producing new sources, five major areas must be considered: 1) source production: nuclear activation and/or radiochemical reaction; 2) welding; 3) quality control: leakage tests; 4) dosimetry and metrology; 5) operational procedures; 6) validation studies. To perform all steps, a multidisciplinary team works together to overcome difficulties. Our major projects are: Iridium-192 pellets: In Brazil there are 150 afterloading machines with pellets that replacement every 4 months (about 450 Iridium-192 sources a year). Our new production line, with the support of IAEA, is in progress, with the hot-cell being installed in a brand-new facility. Iridium-192 wires: In production since 1997, also supported by IAEA. The wire is activated at IPEN’s IEA-R1 reactor for 30 hours with 5x1013 n/cm-2.s-1 neutron flux resulting in 7.1 GBq (192 mCi) maximum activity. Iridium-192 seed: New seed for ophthalmic cancer treatment. The core presented 90% activity homogeneity. We are making the experimental dosimetry and Monte Carlo simulation. Iodine-125 seeds: Largely used in low dose brachytherapy. I-125 binding yield achieved with our new reaction was 90%; Laser welding presented 70% efficiency. Approved in all leakage tests. Our Iodine-125 seeds laboratory production is 90% ready. Other ongoing projects: polymeric Phosphorus-32 source for spinal cancer treatment, Gold-198 nanoparticles for prostate, breast, and liver cancer treatment, Iodine-125 seed as markers for non-palpable cancers, and dosimetry calculations for all new sources. All the projects are advancing, despite national funding difficulties. Withing those, several mSc, Phd, and Post-doc are getting their degrees. We will continue to develop new products hoping to help the Brazilian population fight against cancer. The support of IAEA has proven to be of the utmost importance for these projects not only in direct funding, but in providing knowledge to our team, the possibility to share information with the scientific community, and to form the next generation of scientists.
Synthesis, activation and application testing of gold nanoparticles for nanobrachytherapy
2023 - ROSERO, WILMMER A.A.; BARBEZAN, ANGELICA B.; ROSTELATO, MARIA E.C.M.; SOUZA, CARLA D. de; NOGUEIRA, BEATRIZ R.; ZEITUNI, CARLOS A.
For more than 50 years, the Energy and Nuclear Research Institute IPEN, has been offering solutions to Brazil through nuclear technology. Thus, one of the main areas where IPEN has contributed assertively is medicine. Reaching the level of 32 radiopharmaceuticals and radioactive sources intended both for therapy and for the diagnosis of several pathologies, including cancer, which are obtained with the help of the two nuclear reactors and two cyclotrons present in the institution. The Institute has a team for the development, production and distribution of radioactive sources for brachytherapy, such as 192 Ir wires and 125 I seeds. Brachytherapy is a cancer treatment technique where the radioactive source is placed close to or in contact with the lesion. The great advantage of the technique is to save healthy tissues. Currently, we are working on obtaining nanometric materials that can be applied in the emerging nano brachytherapy, because of its properties and characteristics at the nanometric level, gold has been the subject of studies and tests. Elemental Au gold can be activated 198 Au inside a nuclear reactor, and has β- decay and a half-life of 2.7 days, which makes it ideal for short-term irradiations. In addition, gold in the form of nanoparticles has a completely different chemistry, with gold nanoparticles (AuNPs) being easily functionalized by a large part of molecular and polymeric binders, which may present favorable characteristics for the studies, and together with AuNPs they are able to work synergistically to achieve greater efficiencies. Currently, AuNPs have been successfully functionalized with gum arabic (GA), a coating widely used in the cosmetic and food industry, which is low cost and along with nanoparticles has shown biocompatibility with different cell groups and has been shown to be very stable over time. The project includes studies regarding the synthesis of nanoparticles, coating, cytotoxicity of AuNPs in vitro "cold" (non-radioactive) and the development of activation protocols in the nuclear reactor. In the next phase, after activation, in the reactor, "hot" tests will be performed in vitro and in vivo.
Validation of Fricke xylene gel dosimetry through comparisons between MCNP and TOPAS simulations
2023 - RODRIGUES, PRISCILA; BURIN, ANA; TALACIMON, CRISTHIAN; AMARAL, ILCA MARLI; PEREIRA, JULIO; TEODORO, LARA E.H.; RIGO, MARIA; TAVARES, PAULO; MARTINS, ANNA; RODRIGUES JUNIOR, ORLANDO; SOUZA, CARLA de; ZEITUNI, CARLOS; ROSTELATO, MARIA
Avaliação do método produtivo de placas de epóxi com fósforo-32 para o tratamento do câncer espinhal e intracranial por braquiterapia
2022 - SILVA, J.T.; NOGUEIRA, B.R.; ANGELOCCI, L.V.; SOUZA, C.D.; TEODORO, L.E.; SOUZA, P.D.; RODRIGUES, B.T.; CORREIA, R.W.; SANTOS, H.N. dos; ZEITUNI, C.A.; ROSTELATO, M.E.
A braquiterapia é uma modalidade de radioterapia utilizada no tratamento do câncer. Nessa modalidade, a fonte radioativa é posiciona junto ao tumor ou bem próxima a ele. A dose de radiação é entregue de forma contínua em um período curto de tempo (fontes temporárias) ou em períodos mais longos durante todo o decaimento radioativo do material (fontes permanentes). A maior vantagem da braquiterapia, é o fato da fonte estar bem próxima ao tumor o que significa que a região alvo recebe a maior parte da dose protegendo os tecidos sadios adjacentes à região tumoral. Shtrombakh et. al. trabalharam com césio-137 e verificaram que o uso do epóxi para a imobilização de fontes radiativas ocorreu sem vazamento por dois anos de testes. Pesquisas realizadas nos Estados Unidos por Folkert et. al. mostraram que placas flexíveis incorporadas com fósforo-32 são alternativas para o tratamento de câncer do sistema nervoso central na fase intraoperatória. No presente trabalho foi avaliada a uniformidade da placa de resina epóxi a partir de uma metodologia desenvolvida no Laboratório de fontes para Braquiterapia do IPEN/CNEN- SP. Vários testes foram realizados para determinar o melhor molde para a fabricação da placa. Concluiu-se que o politetrafluoretileno (PTFE), que comercialmente é conhecido como teflon foi o que obteve melhor resultado, devido a facilidade para desenformar a fonte após o processo de cura da resina. As placas de epóxi foram produzidas a resina 2220 e catalisador 3154 (Avipol), à proporção de 2:1 (massa). Para simular o material radioativo, ácido clorídrico (HCl) equivalente a 5 % da massa total (resina + catalisador) é acrescentado. O processo de cura da resina epóxi foi durante 24 h sob temperatura ambiente. As espessuras das placas foram medidas chegando-se a um valor médio de 0,300 mm ± 0,070. As medidas foram efetuadas com micrômetro medindo-se 10 pontos de cada placa. As medidas de largura e comprimento não foram realizadas, pois esses parâmetros não influenciam na uniformidade da dose. Para que a distribuição da atividade do fósforo-32 fosse estipulada, uma simulação por Método de Monte Carlo utilizando o código MCNP foi realizada. A variação máxima de dose ao longo da placa, considerando uma espessura totalmente uniforme de 0,300 mm, resultou em < 0,5 % até 0,5 cm antes da borda. O resultado da simulação mostra que com uma placa de espessura uniforme, a tendência da distribuição de dose seja homogênea. Pautando-se nos resultados, as placas de polímero epóxi se mostram viáveis para o uso em braquiterapia, sendo que o próximo passo do trabalho será os testes com material radioativo, a avaliação por métodos dosimétricos físicos e computacionais.
Production of iodine-125 in nuclear reactors
2011 - ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.; JAE-SON, KWANG; LEE, JUN S.; COSTA, OSVALDO L.; MOURA, JOÃO A.; FEHER, ANSELMO; MOURA, EDUARDO S.; SOUZA, CARLA D.; MATTOS, FABIO R.; PELEIAS JUNIOR, FERNANDO S.; KARAM JUNIOR, DIB
Cancer is one of the worst illnesses in the world and one of the major causes of death in Brazil [1,2]. For this reason, the Nuclear Energy National Commission (CNEN) started a project to produce some medical radioisotopes to treat cancer. One of the main products is the iodine-125 seeds [3]. This iodine seed can be used to treat several kinds of cancer: prostate, lung, eye, brain. As Brazil will construct a new reactor to produce radioisotopes, it is necessary define how the iodine-125 production will carry out [4,5]. The main reaction of this production is the irradiation of the enriched xenon-124 in gaseous form. Xe-124 changed to Iodine-125 by neutron capture following in two decays: Xe-124 (n, y) —• Xe-125m (57s) —• I- 125 or Xe-124 (n, y) —• Xe-125 (19.9 h) —• 1-125. However the production in reactors is the most common technique used, there is one disadvantage to use it: the production of iodine- 126 after several hours of irradiation. Iodine-126 has a half life of 13.1 days and it has some usefulness emitters for medical uses. Iodine-126 is considered a contamination [6]. For all these reasons, the IPEN/CNEN-SP research group decided for two techniques of production: in batch or continuous system. The production in batch consists in a sealed capsule that is placed in the reactor core for around 64 hours. In this type of production, some iodine-126 is produced and a certain quantity of Xe-124 is not activated. Normally, it needs to wait around 5 to 7 iodine-126 half-lives to guarantee the decrease of the activity of the contamination. This time will make Iodine-125 with only 50% till 34% of the initial production. The second technique is the continuous production using a cryogenic system. This technique consists in two capsules: one inside the reactor core and the second one out of the neutron flux. These two capsules will be linked with two cryogenic pumps to guarantee that all iodine-125 produced in the core will be take off the reactor core. The great disadvantage of this technique is the using of two positions in the core of the reactor. Brazil will have only one radioisotope reactor producing. And like there is a huge quantity of materials to be produced, it is not a guarantee the position in the reactor for this production. Besides of that the seeds production in Brazil is only 3000 per month, which demands around 3.5 Ci per month. The batch production produces a low quantity per reactor cycle of iodine-125, but this low quantity can be more than that [2,3].
Preliminary proposal for radioactive liquid waste management in a brachytherapy sources production laboratory
2011 - SOUZA, CARLA D.; VICENTE, ROBERTO; ROSTELATO, MARIA E.C.M.; ZEITUNI, CARLOS A.; MOURA, JOÃO A.; MOURA, EDUARDO S.; MATTOS, FABIO R.; FEHER, ANSELMO; COSTA, OSVALDO L. da; VIANNA, ESTANISLAU B.; CARVALHO, LAERCIO de; KARAN JUNIOR, DIB
Malignant tumors are responsible for a high death rate in the entire world population (1). Prostate cancer is the third most common among men, after skin and lung. The treatment using permanent Iodine-125 seed are too costly, preventing the use in large scale (1) (2). A multidisciplinary team was formed to develop a source of Iodine-125 and assemble a national facility for local production. For the production correct implementation, a plan for radiological protection that has the management of radioactive waste fully specified are necessary. This work has developed an initial liquid waste management proposal. The most important Iodine-125 liquid waste is generated in the first phase of the process, radioactive material fixation. The initial proposal is that the waste is deposited in a 20 L container (2 years to fill). The final activity of this container is 4.93 x 1011 Bq. According to the discharge limits presented in the brazilian's regulation CNEN - NE - 605 - Management of radioactive wastes in radioactive facilities (3) this waste could safely be release to the environment in 3.97 years. In the other hand,if a minimization waste policy will be implemented, the production could becomes more efficient and cheaper. Waste storage at 25 L containers and changing some production parameters results in 3 years waste to be eliminated in 3.94 years. This new plan will optimize the materials used and diminished the waste generation facilitating the management, contributing to a cheaper product.
Iridium-192 seed development for ophthalmic cancer treatment
2011 - ROSTELATO, M.E.C.M.; MATTOS, F.R.; ZEITUNI, C.A.; SOUZA, C.D.; MOURA, J.A.; MOURA, E.S.; FEHER, A.; COSTA, O.L.; PELEIAS JUNIOR, F.S.; MARQUES, J.R.O.; BELFORT NETO, R.
Considered a public health problem in Brazil, cancer is the second leading cause of mortality by disease, representing 13.2% of all deaths in the country [1]. Ophthalmic brachytherapy involves inserting an acrylic plate with radioactive material in the eyes of a patient for treatment of ocular tumors. This work is a partnership between Escola Paulista de Medicina - UNIFESP and the Instituto de Pesquisas Energéticas e Nucleares - IPEN for development and implementation of a cheaper therapeutic treatment for ophthalmic cancer with a iridium-192 source, to attend a greater number of patients. Iridium-192 is produced in nuclear reactor. It has a half-life of 74.2 days and decays by beta emission with average energy of 370 keV.[2,3]. The seed will be a platinum-iridium alloy core (80/20), encapsulated in a titanium tube [4]. This project will be divided into the following steps: characterization of materials by FRX (X-ray fluorescence) e EDS (Energy Dispersive Spectroscopy); iridium irradiation in the nuclear reactor IEA-R1; sealing of iridium-192 seed; leakage tests of iridium-192 source in accordance with standard ISO-9978 (radiation protection- Sealed radioactive sources- Leakage test methods) [5]; metallographic tests and measure the activity of the source. The evaluation for use in the ophthalmic treatment of cancer will be made later.
Improvements in the quality control of iridium-192 wire used in brachytherapy
2011 - COSTA, OSVALDO L.; ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.; MOURA, JOÃO A.; FEHER, ANSELMO; MOURA, EDUARDO S.; SOUZA, CARLA D.; SOMESSARI, SAMIR L.
Brachytherapy is a method used in the treatment of cancerous tumors by ionizing radiation produced by sources introduced into the tumor area, this method seeks a more direct attack to the tumor, thereby maximizing the radiation dose to diseased tissue while minimizing the dose to healthy tissues (1). One of the radionuclides used in brachytherapy is iridium-192. The Radiation Technology Center (CTR) of the Nuclear and Energy Research Institute (IPEN) has produced commercially, since 1998, iridium-192 wires used in low dose rate (LDR) brachytherapy (2). To produce this radionuclide, firstly a iridium-platinum wire is irradiated in the nuclear reactor IEA-R1 for 30 hours with a neutron flux of 5 x 1013 ncm-2s-1, the wire is left to decay by 30 days to remove the main contaminants and then goes through a quality control before being sent to the hospital. In this quality control is checked the radiation homogeneity along each centimeter of the wire (3). To implement this procedure is used a device consisting of an ionization chamber surrounded by a lead shield with a small 1 cm wide slit, linked to the ionization chamber is a voltage source and a Keithley 617 electrometer, 2 minutes is the range used to measure the charge by the electrometer. The iridium wire is considered in accordance when there is no variation greater than 5% between the average measures and the maximum and minimum values. However, due to design features of the measurement system, the wire may appear to the detector through the slit in larger sizes than the ideal, improperly influencing the final quality control. This paper calculates the difference in size of these variations in profile and their influence on the final count, it compares the actual values obtained and describes the improvements made in quality control procedures that provided more accurate measurement data, analyzes the results and suggests changes in devices aimed at further improving the quality control of iridium-192 wires produced at IPEN and used in hospitals in Brazil.
Synthesis, in vitro testing, and biodistribution of surfactant-free radioactive nanoparticles for cancer treatment
2022 - SOUZA, CARLA D. de; BARBEZAN, ANGELICA B.; ROSERO, WILMMER A.A.; SANTOS, SOFIA N. dos; CARVALHO, DIEGO V. de S.; ZEITUNI, CARLOS A.; BERNARDES, EMERSON S.; VIEIRA, DANIEL P.; SPENCER, PATRICK J.; RIBEIRO, MARTHA S.; ROSTELATO, MARIA E.C.M.
New forms of cancer treatment, which are effective, have simple manufacturing processes, and easily transportable, are of the utmost necessity. In this work, a methodology for the synthesis of radioactive Gold-198 nanoparticles without the use of surfactants was described. The nuclear activated Gold-198 foils were transformed into H198AuCl4 by dissolution using aqua regia, following a set of steps in a specially designed leak-tight setup. Gold-198 nanoparticles were synthesized using a citrate reduction stabilized with PEG. In addition, TEM results for the non-radioactive product presented an average size of 11.0 nm. The DLS and results for the radioactive 198AuNPs presented an average size of 8.7 nm. Moreover, the DLS results for the PEG-198AuNPs presented a 32.6 nm average size. Cell line tests showed no cytotoxic effect in any period and the concentrations were evaluated. Furthermore, in vivo testing showed a high biological uptake in the tumor and a cancer growth arrest.
Homogeneity evaluation of phosphorus-32 epoxy plaques to be used in the treatment of spinal and intracranial cancer by brachytherapy
2021 - SILVA, JOSE T. da; SOUZA, CARLA D. de; NOGUEIRA, BEATRIZ R.; ANGELOCCI, LUCAS V.; ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.
In Brachytherapy, radioactive source is positioned close to the tumor. The most important advantage is that the target region receives most of the dose, protecting the healthy tissues adjacent to the tumor region. In order to use these sources, a high dosimetric uniformity must be achieved, so a homogeneous dose delivery can be delivered to the target. In the present work, the consistency of the epoxy resin plate was evaluated using a methodology developed in the laboratory for the production of radiotherapy sources at IPEN / CNEN - SP. Several tests were carried out to determine the best mold for the source manufacture. It was concluded that polytetrafluoroethylene (PTFE), which is commercially known as teflon, obtained the best result, due to the ease unmold of the source after the resin curing process. The epoxy plaques were produced with resin 2220 and catalyst 3154 (Avipol), at a 2:1 mass ratio. To simulate the radioactive material, hydrochloric acid (HCl) equivalent to 5% of the total mass (resin + catalyst) is added. The epoxy resin cured for 24 h at room temperature. The thickness of the plaques was measured reaching an average value of 0.300 mm ± 0.070. The measurements were made with a micrometer, measuring 10 points of each plaque. The measures of width and length were not performed, as these parameters do not influence the uniformity of the dose. In order for the distribution of phosphorus-32 activity to be stipulated, a Monte Carlo Simulation using the MCNP code was performed. The maximum dose variation along the plaque, considering a totally uniform thickness of 0.300 mm, resulted in <0.5% up to 0.5 cm before the edge. The result of the simulation shows that with a uniformly thick plaque, the dose distribution trend is homogeneous. Based on the results, the epoxy polymer plaques are shown to be viable for use in brachytherapy, and the next step of the work will be the tests with radioactive material.