Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-18T13:18:31Z No. of bitstreams: 1 470631 - Texto Parcial.pdf: 431429 bytes, checksum: b5055842a739822ab3818d061be0160a (MD5) / Made available in DSpace on 2015-06-18T13:18:31Z (GMT). No. of bitstreams: 1 470631 - Texto Parcial.pdf: 431429 bytes, checksum: b5055842a739822ab3818d061be0160a (MD5) Previous issue date: 2015-03-26 / Several companies wordwide produce kits with 99mTc labelling for diagnosing neuroendocrine tumors. Aiming at producing this kind of product in Brazil, a formulation was proposed, based on the methodology developed by Guggenberg et ul, using HYNIC-TOC, SnCl2, EDDA, tricine, mannitol and ascorbic acid. For labelling the cold kit, metastable radionuclide technetium (99mTc), produced by a 99Mo generator was used. The product was stored at temperatures of 0 to 8?C and at 25?C before labelling. After the product was labelled, it was kept at room temperature for up to 4 hours. The time of exposure was sufficient to observe the shelf life of the product for each storage method. Considering a radiochemical purity (RCP) of 80%, the product remained stable during the eight-month storage at 0 to 8?C before labelling and up to 4 hours after labelling. Therefore, the use of this product is possible in centers of nuclear medicine for a longer period during the day. / No mundo, diversas empresas produzem kits para diagn?stico de tumores neuroend?crinos para marca??o com 99m Tc. Com a inten??o de nacionalizar esse tipo de produto no Brasil, uma formula??o foi proposta e baseada na metodologia desenvolvida por Guggemberg et al, utilizando HYNIC-TOC, SnCL2, EDDA, tricina, manitol e ?cido asc?rbico. Para marca??o do cold kit, foi utilizado o radionucl?deo tecn?cio metaest?vel(99m Tc), produzido por um gerador de 99Mo. O produto foi armazenado em temperaturasde 0 a 8?C e a 25?C antes da marca??o. Ap?s marca??o do produto, esse foi mantido em temperatura ambiente por at? quatro horas. O tempo de exposi??o foi suficiente para observar a vida do produto em cada m?todo de armazenamento. Considerando-se em limite de PRQ (pureza radioqu?mica) de 80%, o produto se mostrou est?vel durante os oito meses, quando armazenado entre 0 a 8?C antes da marca??o, e at? quatro horas p?s-marca??o. Sendo assim, poss?vel a utiliza??o desse produto, em centro de medicina nuclear, por per?odo mais longo durante o dia.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-05-26T13:22:56Z No. of bitstreams: 1 467668 Texto Parcial.pdf: 567013 bytes, checksum: 1bc3ad00024849f7dae91336da6c5f16 (MD5) / Made available in DSpace on 2015-05-26T13:22:56Z (GMT). No. of bitstreams: 1 467668 Texto Parcial.pdf: 567013 bytes, checksum: 1bc3ad00024849f7dae91336da6c5f16 (MD5) Previous issue date: 2015-03-18 / This work proposes a methodology to obtain the radiopharmaceutical Human Macro-Aggregate Albumin (MAA) for further labeling with the radioisotope technetium-99-metastable (99mTc) and use in diagnostic imaging. The method proposes a process improvement during the manufacturing process for the production of this radiopharmaceutical regarding the established procedures described in international bibliography. 99mTc-MAA is a indispensable radiopharmaceutical, especially for the diagnosis of lung diseases, allowing the evaluation of patient perfusion capacity. This work presents the studies designed to obtain a lyophilized, non-toxic, sterile and pyrogen-free pharmaceutical preparation for intravenous administration. The injectable product reconstituted was characterized by the uniformity of the particles in suspension in relation to the number and size of protein aggregates. The analysis of optical microscopy and scanning electron microscopy (SEM) to check the number and size of particles have showed that none of the aggregates had size larger than 150 microns, therefore, within the clinical application limit. The radiochemical assays demonstrated the production of a product with high radiochemical purity (RQP). The radiochemical characteristics presented by the marked product according to the international pharmacopoeial requirements (QRP > 90%) allowing its use for diagnostic imaging through the technique that uses scintigraphic evaluation of pulmonary perfusion in nuclear medicine by single-photon emission computed tomography (SPECT). / O presente trabalho prop?e uma metodologia para obten??o do radiof?rmaco Macro-Agregado de Soro Albumina Humano (MAA), para posterior marca??o deste com o radiois?topo tecn?cio-99-metaest?vel (99mTc) e, assim, seu uso em diagn?stico por imagem. O m?todo prop?e uma melhoria de processo, em processo, para a manufatura deste radiof?rmaco em rela??o aos processos j? descritos nos comp?ndios internacionais. O 99mTc-MAA ? um radiof?rmaco imprescind?vel, principalmente, para o diagn?stico de patologias pulmonares permitindo a avalia??o da capacidade de perfus?o do paciente. Neste trabalho s?o apresentados os estudos desenvolvidos para a obten??o de uma prepara??o farmac?utica liofilizada de natureza at?xica, est?ril e apirog?nica para administra??o endovenosa. O produto injet?vel reconstitu?do foi caracterizado pela uniformidade do particulado em suspens?o em rela??o ao n?mero e ao tamanho dos agregados proteicos. As an?lises de microscopia ?ptica e de microscopia eletr?nica de varredura (MEV) para verifica??o do tamanho e do n?mero de particulados demonstraram que nenhum dos agregados apresentou tamanho superior a 150 ?m, estando, portanto, dentro do limite m?ximo para aplica??o cl?nica. Os ensaios radioqu?micos demonstraram a produ??o de um produto com elevado grau de pureza radioqu?mica (PRQ). As caracter?sticas radioqu?micas apresentadas pelo produto marcado atendem aos requisitos descritos nas farmacopeias internacionais (PRQ > 90%) permitindo o seu emprego para o diagn?stico por imagem utilizando t?cnica de avalia??o cintilogr?fica pulmonar de perfus?o em medicina nuclear por meio da SPECT (tomografia computadorizada por emiss?o de f?ton ?nico).

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-05-18T12:11:50Z No. of bitstreams: 1 468781 - Texto Parcial.pdf: 384702 bytes, checksum: cde465ffd6e2d42c31965ab814bea74f (MD5) / Made available in DSpace on 2015-05-18T12:11:50Z (GMT). No. of bitstreams: 1 468781 - Texto Parcial.pdf: 384702 bytes, checksum: cde465ffd6e2d42c31965ab814bea74f (MD5) Previous issue date: 2014-04-26 / OBJECTIVE: This paper compares the test results of DMSA renal scintigraphy performed 1, 3 and 6 hours after administration of the radiopharmaceutical in children with clinical suspicion of acute pyelonephritis. MATERIALS E METHODS: DMSA Images were performed 1, 3 and 6 h after tracer injection and evaluated by three nuclear medicine physicians, who rated the kidneys from normal and abnormal, in the three different moments. We used the Criteria for acute pyelonephritis published by The European Association of Nuclear Medicine and the Consensus of normality and its variants, proposed by 30 experts in nuclear nephrology and published in 1999. Moreover, was performed the relative renal function on each patient, for each protocol image, by counting the activity of 99m Tc-DMSA uptake in both kidneys. RESULTS: One hundred sixty nine kidneys from 88 patients were evaluated. There was agreement intra-observer and inter-observer for all comparisons. The prevalence of acute pyelonephritis was 22,7%. There were no statistically significant changes in function calculation on the three proposed protocols. CONCLUSION: There was no statistically significant difference in the images taken at 1, 3 and 6h in the scintigraphic evaluation of acute pyelonephritis in children up to ten years. Also do not change the functional indices in the three moments. / OBJETIVO: Esse trabalho compara os resultados dos exames de cintilografia renal com DMSA realizados 1, 3 e 6h ap?s a administra??o do radiof?rmaco em crian?as com suspeita cl?nica de pielonefrite aguda. MATERIAIS E M?TODOS: As imagens de DMSA foram realizadas 1, 3 e 6h ap?s a inje??o do radiof?rmaco e avaliadas por tr?s m?dicos nucleares, que classificaram os rins em normal ou anormal, nos tr?s momentos diferentes, isoladamente. Foram usados os crit?rios para pielonefrite aguda publicados pela Associa??o Europeia de Medicina Nuclear e o Consenso de normalidade e suas poss?veis variantes, proposto por 30 especialistas em nefrologia nuclear e publicado em 1999. Al?m disso, foi realizado o c?lculo da capta??o renal relativa de cada paciente, para cada protocolo de imagem, atrav?s da contagem da atividade de capta??o do 99mTc-DMSA em cada rim. RESULTADOS: foram avaliados 169 rins de 88 pacientes. Houve concord?ncias intra-observadores e inter-observadores para todas as compara??es realizadas. A preval?ncia de pielonefrite aguda foi de 22,7%. N?o houve altera??es estatisticamente significativas nos c?lculos das fun??es relativas nos tr?s protocolos propostos. CONCLUS?O: N?o h? diferen?a estatisticamente significativa nas imagens realizadas em 1, 3 e 6h na avalia??o cintilogr?fica de pielonefrite aguda em crian?as de zero a dez anos com quadro cl?nico de ITU. Tamb?m n?o variam os ?ndices funcionais nos tr?s momentos.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-19T11:53:50Z No. of bitstreams: 1 470623 - Texto Parcial.pdf: 1446399 bytes, checksum: 3695d8ae78a5226ff8ef00bf63332a89 (MD5) / Made available in DSpace on 2015-06-19T11:53:50Z (GMT). No. of bitstreams: 1 470623 - Texto Parcial.pdf: 1446399 bytes, checksum: 3695d8ae78a5226ff8ef00bf63332a89 (MD5) Previous issue date: 2015-03-06 / The gallium-68 (68Ga), an extremely promising positron-emitting radionuclide, has major advantages when compared to other radionuclides used in Positron Emission Tomography (PET), like fluor-18 and carbon-11. Differently from these PET radionuclides, gallium-68 is available from a 68Ge/68Ga generator, which allows its distribution even in nuclear medicine centers located far from cyclotrons. In recent years, an increase in the use of 68Ga PET radiopharmacy was observed around the world. However, in Brazil there is still only four centers with this technology available, mainly due to the difficulty in the access. Radiopharmaceuticals used for diagnostics are scarcely accessible in our country. Among radiopharmaceuticals most used around the world are the DOTA-peptides, somatostatin analogs for the diagnosis of neuroendocrine tumors. Considering the present scenario, this study aimed to develop a diagnostic kit of DOTA-TOC for labeling with 68Ga, with high radiolabeling yield and high radiochemical purity, thus stimulating the use of this innovative radionuclide in Brazil. / O G?lio-68 (68Ga), um radionucl?deo emissor de p?sitrons extremamente promissor, apresenta grandes vantagens quando comparado a outros radionucl?deos para uso em Tomografia por Emiss?o de P?sitrons (PET), como o fl?or-18 e carbono-11. Diferentemente destes radionucl?deos, que s?o produzidos em c?clotrons, o 68Ga ? produzido em gerador a partir de um radionucl?deo de longa vida ?til, o Germ?nio-68 (68Ge), o que permite sua distribui??o mesmo em centros de Medicina Nuclear que se localizem muito distantes de c?clotrons. Apesar de a radiofarm?cia com 68Ga ter se desenvolvido muito nos ?ltimos anos em todo o mundo, o Brasil ainda tem somente quatro centros que possuem essa tecnologia dispon?vel. Isto se deve especialmente ? dificuldade de utiliza??o, j? que os pept?deos necess?rios para a marca??o dos radiof?rmacos s?o importados. Dentre os radiof?rmacos que est?o sendo mais utilizados no mundo, destacam-se os DOTA-pept?deos, an?logos da somatostatina utilizados no diagn?stico de tumores de origem neuroend?crina. Diante do cen?rio atual, este trabalho teve por objetivo o desenvolvimento de um kit diagn?stico de DOTA-TOC para marca??o com 68Ga, com altos rendimento de marca??o e pureza radioqu?mica, e, assim, estimular a utiliza??o desse radionucl?deo inovador no Brasil.

Made available in DSpace on 2015-04-14T13:33:05Z (GMT). No. of bitstreams: 1 448602.pdf: 5444949 bytes, checksum: 5f077f7aa23c0ec642d7726b401ada78 (MD5) Previous issue date: 2013-03-04 / OBJECTIVE: To calculate the frequencies of acute pyelonephritis and renal scarring in youngers than two years old through scintigraphy with 99mTcDMSA with first episode of UTI in a Brazilian university hospital and comparing with international literature. MATERIALS AND METHODS: We reviewed reports scintigraphy of youngers than two years old who underwent scintigraphy with 99mTcDMSA in a university hospital in Rio Grande do Sul, between 2006 and 2009 to search for APN and renal scarring. It was also revised the presence of vesicoureteral reflux, early use of antibiotics, and comorbidities that were recorded in e lectronic records. The sample size calculation was based on a systematic review study and obtained a minimum of 147 patients. We excluded patients with no electronic record. RESULTS: 157 children met the inclusion criteria, where 48 had APN and 8 of these had renal scars. There was no statistical difference in the association of VUR and APN (p=1.0) as well as among all comorbidities (p=0.470). There was no significance relation to early use of antibiotics and APN (p=0.130) and renal scarring (p=0.720). CONCLUSION: The frequency of renal scarring and APN obtained agree with the results of most studies. / OBJETIVO: Calcular as frequ?ncias de pielonefrite aguda (PNA) e cicatriz renal em pacientes menores de dois anos com cintilografia renal com 99mTcDMSA com primeiro quadro de ITU em hospital universit?rio brasileiro comparando com dados da literatura internacional. MATERIAIS E M?TODOS: Foram revisados laudos cintilogr?ficos de crian?as menores de dois anos de idade que realizaram cintilografia renal com 99mTcDMSA em um hospital universit?rio de no Rio Grande do Sul, entre 2006 e 2009 para pesquisa de PNA/cicatriz renal. Revisouse a presen?a de refluxo v?sicoureteral (RVU), uso precoce de antibi?tico, e presen?a de comorbidades que constassem nos prontu?rios eletr?nicos. Calculouse a amostra baseado num estudo de revis?o sistem?tica e obtevese um m?nimo de 147 pacientes. Excluiu-se pacientes sem registro eletr?nico. RESULTADOS: 157 crian?as preencheram crit?rios de inclus?o do estudo, 48 tiveram PNA e 8 destes apresentaram cicatriz renal. Nem a idade e g?nero dos pacientes apresentaram associa??o significativa com PNA (p=0,405; p=0,124 respectivamente). N?o houve diferen?a estat?stica nas associa??es de RVU e PNA (p=1,0) e outras comorbidades (p=0,470); e em rela??o ao uso precoce de antibi?tico com PNA (p=0,130) e cicatriz renal (p=0,720). CONCLUS?O: As frequ?ncias de PNA e cicatriz renal obtidas concordam com os resultados da maioria dos estudos publicados

Made available in DSpace on 2015-04-14T13:35:49Z (GMT). No. of bitstreams: 1 452036.pdf: 1676220 bytes, checksum: 099b6754a6aea6b267cc1b8e2ae71a36 (MD5) Previous issue date: 2013-07-24 / Molecular Imaging is a technique that allows visualization, characterization and quantification of biochemical processes in a molecular and cellular level, in humans and other live organisms. Among all the technics available, it s possible to highlight PET (Positron Emission Tomography), which needs the administration of a radiotracer in the organism to be studied. Radiotracers or radiopharmaceuticals are molecules that possess a radioactive element in their composition. Nowadays, the most used PET radiopharmaceutical is fluorodeoxyglucose (18F) or [18F]FDG. This molecule is a glucose analogue that accumulates inside the cell, allowing glucose metabolism visualization. However, considering the use of glucose by the brain as its main energy source, this radiopharmaceutical accumulates in high rates in the normal brain, making difficult to see pathological processes. In order to visualize more specific alterations in the brain, many others radiotracers can be used, for example flumazenil (18F). Flumazenil (FMZ) shows high affinity for the benzodiazepine site in the GABAA receptor, acting as competitive antagonist. It s already known that GABAA receptors play a key role in neuronal excitability control, and expression deficiencies in these receptors are involved in many neurological and psychiatric disorders, such as epilepsy, anxiety, depression, schizophrenia, etc. Regarding epilepsy, it is believed that in the epileptogenic foci the GABAA receptor expression is reduced, the brain region where seizures start. For this reason, the aim of this work was to study flumazenil (18F) synthesis, as well as its purification and quality control analysis, in order to produce a molecule that can be used to localize the epileptogenic foci. The fluoride ion (18F-) was produced using PET Trace 16 MeV cyclotron from GE Healthcare, through the nuclear reaction 18O(p,n)18F, through the irradiation of enriched 18O water with accelerated protons. The flumazenil (18F) synthesis was performed in the automated synthesis module TRACERlab FX F-N from GE Healthcare, by nucleophilic aromatic substitution reaction. The established ideal reaction conditions were 145?C for 15 minutes, and 6,2mg precursor mass. The 18F- incorporation degree in the flumazenil molecule was 72?6% (n = 5), verified by reaction mixture analysis. In the last step flumazenil (18F) was purified through high performance liquid chromatography (HPLC) and reserve-phase tC18 cartridge, obtaining a product with a purity higher than 99%. The radionuclidic purity and identity were analyzed by gamma ray spectroscopy and half-life evaluation. Radiochemical purity was verified using thin layer chromatography (TLC) and HPLC. The chemical purity tested the presence of kryptofix 2.2.2, through a colorimetric test, and residual solvents (ethanol and acetonitrile) through gas chromatography (GC). The pH was verified using strips. All the results complied with the pharmacopeia using [18F]FDG as reference. Synthesis time was 80 minutes including purification steps and the overall yield was 9.3% (decay corrected). The radiopharmaceutical stability was analyzed for 8 hours, and no impurities were detected in this period. The method developed showed to be viable to produce flumazenil (18F), which can be used in pre-clinical and clinical studies in the future. The knowledge acquired with this work will allow the improvement of this technology in the country, and the research of new radiotracers for PET/CT imaging. / A Imagem Molecular ? uma t?cnica que permite a visualiza??o, caracteriza??o e quantifica??o de processos bioqu?micos a n?vel molecular e celular, em humanos e outros organismos vivos. Dentre as tecnologias dispon?veis, destaca-se o PET (Positron Emission Tomography - Tomografia por Emiss?o de P?sitrons) que necessita da administra??o do radiotra?ador ao organismo a ser estudado. Radiotra?adores ou radiof?rmacos s?o mol?culas que possuem um elemento radioativo em sua composi??o. Atualmente, o radiof?rmaco mais utilizado em PET ? o fludesoxiglicose (18F) ou [18F]FDG. Esta mol?cula ? um an?logo da glicose, que se acumula no interior da c?lula, permitindo a visualiza??o do metabolismo da glicose. Entretanto, considerando que o c?rebro utiliza basicamente a glicose como fonte de energia, este radiof?rmaco se acumula em altas taxas no c?rebro normal, dificultando a visualiza??o de processos patol?gicos. A fim de visualizar altera??es patol?gicas mais espec?ficas no c?rebro, v?rios outros radiotra?adores podem ser utilizados, como por exemplo o flumazenil (18F). O flumazenil (FMZ) apresenta alta afinidade pelo local de liga??o de benzodiazep?nicos do receptor GABAA, atuando como antagonista competitivo. Sabe-se que os receptores GABAA possuem um papel chave no controle da excitabilidade neuronal e que defici?ncias na express?o destes receptores est?o envolvidas em um grande n?mero de patologias neurol?gicas e psiqui?tricas, como epilepsia, ansiedade, depress?o, esquizofrenia e etc. Com rela??o a epilepsia, acredita-se que exista uma diminui??o da express?o dos receptores GABAA no foco epileptog?nico, regi?o do c?rebro geradora das crises epil?pticas. Desta forma, o objetivo deste trabalho foi estudar a s?ntese do flumazenil (18F), bem como sua purifica??o e as an?lises de controle de qualidade, visando produzir uma mol?cula que auxilie na localiza??o do foco epileptog?nico. O ?on fluoreto (18F-) foi produzido no c?clotron PET Trace 16 MeV da GE Healthcare, atrav?s da rea??o nuclear 18O(p,n)18F, decorrente da irradia??o da ?gua enriquecida com 18O pelos pr?tons acelerados. A s?ntese do flumazenil (18F) foi realizada no m?dulo automatizado TRACERlab FX F-N da GE Helthcare, atrav?s de uma rea??o de substitui??o nucleof?lica arom?tica. As condi??es ideais de rea??o foram estabelecidas em 145?C durante 15 minutos, sendo que a massa do precursor foi de 6,2mg. A taxa de incorpora??o do 18F- na mol?cula do flumazenil foi de 72?6% (n = 5), verificado atrav?s da an?lise da mistura de rea??o. Na fase final o flumazenil (18F) foi purificado atrav?s de cromatografia l?quida de alta efici?ncia (CLAE) e cartucho de fase-reversa tC18, obtendo-se um produto com grau de pureza superior a 99%. A pureza e identidade radionucl?dica foram avaliadas atrav?s de espectroscopia de raios gama e do tempo de meia-vida. A pureza radioqu?mica foi verificada por cromatografia em camada delgada (CCD) e CLAE. Na an?lise da pureza qu?mica verificou-se a presen?a de kryptofix 2.2.2, atrav?s de teste colorim?trico, e solventes residuais (etanol e acetonitrila) por cromatografia gasosa (CG). O pH foi analisado utilizando fitas. Os resultados obtidos foram dentro dos limites estabelecidos pela farmacop?ia levando em considera??o o [18F]FDG. O tempo total de s?ntese foi de 80 minutos e o rendimento total foi de 9,3% (corrigido pelo decaimento). A estabilidade do radiof?rmaco foi analisada durante 8 horas, sendo que nenhuma impureza foi detectada neste per?odo. O m?todo desenvolvido mostrou ser vi?vel para produ??o do flumazenil (18F), podendo este ser futuramente utilizado em estudos pr?-cl?nicos e cl?nicos. Os conhecimentos adquiridos com este trabalho permitir?o o avan?o desta tecnologia no pa?s, e a pesquisa de novos radiotra?adores para a realiza??o de exames PET/CT.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-07-26T14:25:23Z No. of bitstreams: 1 DIS_MARCOS_VINICIUS_FORTES_ALBA_COMPLETO.pdf: 1333852 bytes, checksum: c687fbcabc052faa5ed3567c986640e9 (MD5) / Made available in DSpace on 2016-07-26T14:25:23Z (GMT). No. of bitstreams: 1 DIS_MARCOS_VINICIUS_FORTES_ALBA_COMPLETO.pdf: 1333852 bytes, checksum: c687fbcabc052faa5ed3567c986640e9 (MD5) Previous issue date: 2016-02-15 / Nuclear Medicine enables, among other things, the visualization, characterization and quantification of biochemical processes, metabolism, biomarkers and receptors in vivo by molecular imaging. One of the methods of functional imaging available in this area is Positron Emission Tomography (PET), which depends on the administration of a radiopharmaceutical in the studied organism. One disease that can be studied by PET scan is multiple sclerosis (MS) through the access to the TSPO (Translocator protein) receptors density. The radiopharmaceutical [11C]-(R) -PK11195 has high affinity and selectivity for these receptors, which are increased in activated microglia cells in the case of MS. Therefore, the objective of this study was to develop and to validate the production process (synthesis, purification and quality control) of the radiotracer [11C]-(R)-PK11195 in the Radiopharmaceutical Production Center of the Brain Institute of Rio Grande do Sul (BraIns), allowing performing PET scans for the study of MS. The radioisotope was produced in the 16 MeV PETrace cyclotron (GE Healthcare) as [11C]CO2 via the nuclear reaction 14N (p, ?)11C after the bombardment of a gaseous target containing N2 and 0.5% of O2 with protons. The production was performed in the equipment TRACERlab FX-C Pro (GE Healthcare) to meet the requirements of Good Manufacturing Practices (GMP). The radiopharmaceutical quality control was carried out at the BraIns Quality Control Laboratory and the final product was tested for Identity and Radionuclidic Purity, Radiochemical Purity, Specific Activity, Residual Solvents, pH, Sterility, the Filtration Membrane Integrity and Bacterial Endotoxins. The synthesis was performed through the methylation of the precursor (R)-[N-desmethyl]PK11195 using [11C]CH3I (methyl iodide labeled with carbon-11) under the defined optimal conditions: 400 uL of dimethyl sulfoxide (DMSO), approximately 1 mg of precursor, approximately 10 mg of potassium hydroxide (KOH) at 40 ?C for 1 minute. The reaction mixture was then neutralized with 1 mol.L-1 hydrochloric acid and diluted with mobile phase (76% acetonitrile and 24% Milli-Q water). The diluted mixture was injected into a semi-preparative HPLC system for purification. Solid phase extraction (through Sep-Pak C18 cartridges - Waters) was used to remove the solvent. Product elution and formulation was conducted with 0.7 mL of ethanol and 6.3 ml of 0.9% saline (sterile and pyrogen free). Sterilization was performed by filtration on a 0.22 ?m pore membrane and, as well as the filling process, was carried out under laminar flow. The process steps could be optimized and fitted to the equipments and laboratories structure. Radiochemical yield of the process in relation to the [11C ]CH3I start activity was 15.5 ? 2.4 % ( 7471.5 ? 1283.8 MBq ; n = 39 ) . All batches were approved according to the specifications defined and tested in the quality control, reaching Radiochemical Purity levels greater than 99% and a Specific Activity of 39.7 ? 11.1 GBq / micromol , 10 minutes before the injection. All analytical methods were validated and met the requirements established by current regulations. Three consecutive batches were produced and approved by the quality control, so the process could be considered validated. The developed process was suitable for production of adequate doses of the radiopharmaceutical [11C]-(R)-PK11195 for clinical use at BraIns. The production of the radiopharmaceutical labeled with carbon-11 at the institute provides an additional tool for improving health services in the country and to improve the life quality of the patients. / A medicina nuclear possibilita, dentre outras coisas, a visualiza??o, caracteriza??o e quantifica??o de processos bioqu?micos, metab?licos, biomarcadores e receptores, in vivo, atrav?s da imagem molecular. Dentre as modalidades de imagem funcional dispon?veis nesta ?rea est? a Tomografia por Emiss?o de P?sitrons (PET), que depende da administra??o de um radiof?rmaco no organismo estudado. Uma das doen?as pass?veis de estudo atrav?s do exame PET ? a esclerose m?ltipla (EM), atrav?s do acesso ? densidade de receptores TSPO (Prote?na Translocadora). O radiof?rmaco [11C]-(R)-PK11195 possui alta afinidade e seletividade por estes receptores, aumentados nas c?lulas ativadas da micr?glia nos casos de EM. Portanto, o objetivo deste trabalho foi desenvolver e validar o processo produtivo (s?ntese, purifica??o e controle de qualidade) do radiof?rmaco [11C]-(R)-PK11195 no Centro de Produ??o de Radiof?rmacos do Instituto do C?rebro do RS (InsCer), possibilitando a realiza??o de exames PET para o estudo da EM. O radiois?topo foi produzido no C?clotron PETrace 16 MeV (GE Healthcare) na forma de [11C]CO2 atrav?s da rea??o nuclear 14N(p,?)11C, por meio do bombardeamento com pr?tons do alvo gasoso contento N2 e 0,5 % de O2. A produ??o foi realizada no equipamento TRACERlab FX-C pro (GE Healthcare) atendendo ?s exig?ncias de Boas Pr?ticas de Fabrica??o (BPF). O controle de qualidade do radiof?rmaco foi realizado no Laborat?rio de Controle de Qualidade do InsCer e o produto acabado foi submetido ?s an?lises de Identidade e Pureza Radionucl?dica, Pureza Radioqu?mica, Atividade Espec?fica, Solventes Residuais, pH, Esterilidade, Integridade da Membrana Filtrante e Teor de Endotoxinas. A s?ntese foi realizada atrav?s da metila??o do precursor (R)-[N-desmetil]PK11195 utilizando o [11C]CH3I (iodeto de metila marcado com carbono-11) sob as condi??es ?timas definidas: 400 ?L de dimetilsulf?xido (DMSO), aproximadamente 1 mg de precursor, aproximadamente 10 mg de hidr?xido de pot?ssio (KOH), a 40 ?C durante 1 minuto. A mistura de rea??o foi posteriormente neutralizada com ?cido clor?drico 1 mol.L-1 e dilu?da com fase m?vel (acetonitrila 76 % e ?gua Milli-Q 24 %). A mistura dilu?da foi injetada em sistema CLAE semi-preparativo para purifica??o. Extra??o de fase s?lida (atrav?s de cartuchos SepPak C18 ? Waters) foi utilizada para remo??o do solvente. A elui??o e formula??o do produto foi realizada com 0,7 mL de etanol e 6,3 mL de solu??o salina 0,9 % (est?ril e livre de pirog?nios). A esteriliza??o foi realizada atrav?s de filtra??o em membrana de poro de 0,22 ?m e, assim como o envase, ocorreu em fluxo laminar. As etapas do processo foram otimizadas e adequadas aos equipamentos e estrutura dos laborat?rios. O rendimento radioqu?mico do processo em rela??o ? atividade de [11C]CH3I de partida foi de 15,5?2,4 % (7471,5?1283,8 MBq; n=39). Todos os lotes produzidos foram aprovados quanto ?s especifica??es definidas e testadas no controle de qualidade, atingindo Pureza Radioqu?mica maior que 99 % e uma Atividade Espec?fica de 39,7?11,1 GBq/?mol, 10 minutos antes da inje??o. Todas as metodologias anal?ticas foram validadas e atenderam os crit?rios estabelecidos pela norma vigente. Tr?s lotes consecutivos foram produzidos e aprovados no controle de qualidade e o processo p?de ser considerado validado. O processo desenvolvido se mostrou adequado para produ??o do radiof?rmaco [11C]-(R)-PK11195 em doses suficientes para realiza??o de exames em pacientes no InsCer. A produ??o do radiof?rmaco marcado com carbono-11 no instituto disponibiliza mais uma ferramenta para melhoria dos servi?os de sa?de no pa?s e para melhoria da qualidade de vida dos pacientes.