JOÃO AUGUSTO MOURA

JOÃO AUGUSTO MOURA

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Possui graduação em Tecnologia em saúde pela Faculdade de Tecnologia de Sorocaba (2005). Mestrado em Tecnologia Nuclear pela Universidade de São Paulo (2009). Doutorado em Tecnologia Nuclear pela Universidade de São Paulo (2015). Tem experiência na área de Tecnologia Nuclear, com ênfase em produção de fontes para radioterapia. Atualmente trabalha em pesquisa e desenvolvimento no Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP). (Texto extraído do Currículo Lattes em 8 maio 2023)

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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.
Challenges in iodine-125 sources production for cancer treatment
2023 - FEHER, ANSELMO; BAPTISTA, TATYANA S.; ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.; MOURA, JOÃO A.
There is a great challenge the implantation on assurance quality system in the brachytherapy sources production. It involves tofulfill the Good Manufacturing Practices (GMPs) requirements, involving the process validation and of all supporting activities such as cleaning and sanitization. The purpose of this work was to execute a process validation in the iodine-125 seeds production on Radiation Technology Center located at IPEN- Brazil. Besides this, the sanitization was to evaluate the effectiveness of different surface cleaning products, determining the best to reduce radiological contamination to acceptable levels during the sources production, according to legislation. The fabrication process was performed three times for evaluation. The parameters evaluated in this study were: the source welding efficiency and the leakage tests results (immersion test). The welding efficiency doesn’t have an established parameter, since is visually evaluated by the operator, and the leakage detection has to be under 5 nCi / 185 Bq, accordingly with the ISO 9978. In the relation of sanitization, it was established a cleaning program for three production lots of iodine 125 seeds using three types of sanitizers: Lot 1 with extran 1/1 (v/v), Lot 2 with hydrogen peroxide 6% and Lot 3 with sodium hydroxide 1M. Each lots contained seven iodine 125 seeds and was immersed in the sanitizer for 1 hour and then two washes with distilled water. An activity detected in each lots does not exceed 0,2 kBq (˭5nCi). The observed values on process validation were: 75% welding efficiency and 32% leakage detection. Although established values for the global efficiency aren’t available in the literature, the results showed high consistency and acceptable percentages, especially when other similar manufacturing processes are used in comparison (average 85-70% found in the literature for other similar metallic structures). According to results of sanitization, the best choice for remove de surface contamination was peroxide hydrogen. Further testing should ensure the sanitizer's choice is based not only on the removal of surface contamination, but also this sanitizer does not leave residues requiring further rinsing with distilled water. Those values will be important data when drafting the validation document and to follow the Good Manufacturing Practices (GMPs).
How to select a dosimeter?
2023 - MEDEIROS, ILCA M.A.M.; SILVA, ANA C.K. de S.; TALACIMON, CRISTHIAN F.; MOURA, JOAO A.; TEODORO, LARA E.H.; RIGO, MARIA E.Z.; RODRIGUES, PRISCILA S.; ROSERO, WILMMER A.A.; ROSTELATO, MARIA E.C.M.; ZEITUNI, CARLOS A.
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.
A proposal of process validation in the implementation of Good Manufacturing Practices in brachytherapy sources production
2021 - BAPTISTA, TATYANA S.; FEHER, ANSELMO; RODRIGUES, BRUNA T.; ZEITUNI, CARLOS A.; MOURA, JOÃO A.; ROSTELATO, MARIA E.C.M.
New laboratories for brachytherapy sources production are being implemented in our facility at IPEN, in São Paulo. A great challenge implementing a production laboratory is to comply with the Good Manufacturing Practices (GMPs), which involves process validation and all supporting activities such as cleaning and sanitization. Much more than compliance with regulatory guidelines, required for certification and inspections, a validation builds large process knowledge, provides possibilities for optimization and improvement, increasing the degree of maturity of all people involved and the quality system. The process validation results in a document that certifies that any procedure, process, equipment, material, operation, or system leads to the expected results. This work focused on the new laboratory, been assembled to produce small iodine-125 seeds. The process validation was performed three times for evaluation. The parameters evaluated in this study were: the source welding efficiency and the leakage tests results (immersion test). The welding efficiency does not have an established parameter, since is visually evaluated by the operator, and the leakage detection must be under 5 nCi / 185 Bq, accordingly with the ISO 9978. We observed values were average 79-87% production efficiency and leakage tests were under 5 nCi/seed. Although established values for the global efficiency aren’t available in the literature, the results showed high consistency and acceptable percentages, especially when other similar manufacturing processes are used in comparison (average 85-70% found in the literature for other similar metallic structures). Those values will be important data when drafting the validation document and to follow the Good Manufacturing Practices (GMPs).
Gamma spectrometry of iodine-125 produced in IEA-R1 nuclear reactor, using HPGe detector and fixation into epoxy matrix disc
2021 - COSTA, OSVALDO L. da; SOUZA, DAIANE C.B. de; CASTANHO, FABIO G.; FEHER, ANSELMO; MOURA, JOÃO A.; SOUZA, CARLA D.; OLIVEIRA, HENRIQUE B.; MADUAR, MARCELO F.; ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.
Few places in the world produce iodine-125. In Brazil, the first production was achieved by using the IEA-R1 nuclear reactor located at Nuclear and Energy Research Institute – IPEN. To verify the quality of iodine-125 produced, and the amount of contaminants such as iodine-126, cesium-134 and caesium-137 among others, iodine-125 samples were immobilized into epoxy matrix disc, with the same geometry of a barium-133 reference radioactive source, used to calibrate an HPGe detector. The HPGe detector has a thin carbon composite window, which allows measure the iodine-125 photopeaks, between 27.1 and 35.4 keV. The method employed here was successful in producing and measurement of iodine-125.
New core configuration for the fabrication of 125I radioactive sources for cancer treatment
2020 - SOUZA, CARLA D. de; ZEITUNI, CARLOS A.; FEHER, ANSELMO; MOURA, JOÃO A.; COSTA, OSVALDO L. da; ANGELOCCI, LUCAS V.; ROSTELATO, MARIA E.C.M.
In order to provide prostate brachytherapy treatment for more Brazilian men, IPEN is building a laboratory for the manufacture of radioactive sources. The new methodology for the production of iodine-125 seeds with yield 71.7% ± 5.3%. Points of importance were evaluated/discussed: photo-sensibility, reaction vial type, the substitution for iodine-131, pH, and solution volume. The surface was analyzed by FTIR and EDS. At the end, a Monte Carlo-MCNP6 simulation was performed to evaluate the TG-43 parameters.