STAUFEN1 (STAU1) est une protéine de liaison à l’acide ribonucléique (ARN) double brin jouant un rôle important dans le contrôle post-transcriptionnel de nombreux ARN messager (ARNm). Sa déplétion diminue la prolifération des cellules non cancéreuses en altérant les transitions G1/S et G2/M. En revanche, Ceci n’a aucun impact sur la prolifération des cellules tumorales. La déplétion de STAU1 module le niveau d’expression des transcrits et/ou des protéines impliquées dans la régulation des points de contrôle des transitions de phase. Notamment, STAU1 module le niveau d’expression de la protéine CDK4 ainsi que l’abondance de l’ARNm E2F1, deux régulateurs indispensables de la transition G1/S. Le transcrit de ces deux gènes possède un site de liaison à STAU1 ou STAU1 binding site (SBS) dans la région codante ou coding sequence (CDS) et dans la région non codante en 3’ (3’UTR), respectivement. Cependant, l’importance de la liaison de STAU1 à ces transcrits n’a pas encore été étudiée. Étonnamment, la sensibilité des cellules non tumorales et tumorales à l’expression de STAU1 est inversée lors de la surexpression de STAU1. En effet, sa surexpression altère l’entrée en mitose des cellules cancéreuses et diminue leur prolifération, alors qu’elle n’a aucun effet sur la prolifération des cellules non tumorales. Lors de la mitose, STAU1 s’associe au fuseau mitotique (FM), ce qui lui permet de localiser des ARNm et de contrôler leur séquestration et/ou leur traduction locale. Cependant, le mécanisme qui permet à STAU1 de lier le FM est encore inconnu. Pour ce mémoire, nous avons donc poursuivi deux objectifs. Le premier but est de comprendre la régulation post-transcriptionnelle médiée par STAU1 des transcrits essentiels à la transition G1/S chez les cellules non tumorales. Notre hypothèse est que STAU1 par sa liaison directe à ses transcrits cibles via le SBS module leur expression. Pour ce faire, des cellules de type sauvage ou déplétées en STAU1 étaient transfectées par des plasmides exprimant les transcrits de CDK4 et d’E2F1 contenant un SBS endogène ou muté de telle sorte qu’il ne reconnait plus STAU1. L’expression des protéines CDK4 et E2F1 est dosée par un essai luciférase ou un immunobuvardage de type western ou western blot (WB). Nous avons observé que STAU1 régule négativement et positivement l’expression endogène de CDK4 et d’E2F1, respectivement, ce qui contribue au passage de la transition G1/S, donc à la prolifération cellulaire non tumorale. Les essais luciférases ont confirmé le rôle de STAU1 dans la régulation positive d’E2F1 lorsque liée au SBS dans le 3’UTR du transcrit E2F1. Malheureusement, les plasmides utilisés pour l’expression de CDK4 se sont avérés non fonctionnels, ce qui nous a forcés à mettre de côté cette expérience. Le deuxième but est d’étudier les déterminants qui régulent la localisation de STAU1 au FM chez les cellules tumorales. Pour ce faire, la localisation de STAU1 ou des mutants au FM est détectée par WB à partir de préparations des FM purifiés. Nos données montrent que le déterminant est composé de plusieurs acides aminés (aa) situés entre le 26ème et 37ème aa du côté N-terminal de la protéine STAU1. En somme, nos résultats montrent les différents rôles de STAU1 dans les cellules tumorales vs cellules non tumorales. De ce fait, STAU1 pourrait être une cible thérapeutique spécifique potentielle dans le traitement du cancer. / STAUFEN1 (STAU1) is a double stranded RNA binding protein that plays an important role in the post-transcriptional control of many mRNAs. Its depletion decreases the proliferation of non-cancer cells by altering G1/S and G2/M transitions. In contrast, this has no impact on the proliferation of tumor cells. The decrease of STAU1 expression modulates the level of transcripts/proteins of several genes involved in phase transition checkpoints, including CDK4 and E2F1, two essential regulators in G1/S transition. In addition, CDK4 and E2F1 transcripts have a STAU1 binding site (SBS) in the coding sequence (CDS) and the non-coding region in 3’ (3’UTR), respectively. However, the molecular consequence of STAU1 association with the SBS is not yet studied. Surprisingly, the sensibility of non-cancer and cancer cells to STAU1 expression is reversed following STAU1 overexpression. Indeed, its overexpression alters the entry into mitosis of cancer cells and decreases their proliferation, while it has no effect on non-cancer cells. During mitosis, STAU1 associates with the mitotic spindle, which allows it to localize mRNAs and other non-coding RNAs. STAU1 likely controls their sequestration and/or local translation during mitosis. However, the molecular determinant involved in STAU1-spindle association is still not known. Therefore, for this master thesis, we had two objectives. The first goal is to understand the post-transcriptional regulation mediated by STAU1 on transcripts that are essential for G1/S transition in non-tumor cells. Our hypothesis is that STAU1, by its direct binding to the SBS of its target transcripts, modulates their expression. To do this, plasmids coding for CDK4 and E2F1 containing a wild-type or mutated SBS that does not recognized STAU1 were transfected in wild-type and STAU1-depleted cells. Expression of CDK4 and E2F1 was detected by dual luciferase assay and western blot (WB). Our results first indicate that STAU1 negatively and positively regulates the endogenous expression of CDK4 and E2F1, respectively, which contributes to the passage of G1/S transition, and therefore to the proliferation non-tumor cells. Then, the luciferase assays confirm the role of STAU1 in E2F1 expression, depending on STAU1 binding to E2F1 SBS in its 3’UTR. Unfortunately, the plasmids used for CDK4 expression turned out to be non-functional. The second goal is to identify the molecular determinants responsible for the localization of STAU1 to the mitotic spindle in tumor cells. To this end, the localization of STAU1 or of several mutants was measured by WB using purified spindle preparations. Our data show that the determinant is composed of several amino acids (aa) located between the 26th and 37th aa at the N-terminal end of STAU1. In summary, our results show the different roles of STAU1 in tumor and non-tumor cells. Therefore, STAU1 could be a potential specific therapeutic target in cancer treatments.

Introduction: The presence of circulating tumor cells (CTC) in the peripheral blood has been associated with worse prognosis and early relapse in breast cancer patients. CTC determination in the peripheral blood has been considered as a liquid biopsy. The aim of this project was to analyze the presence of CTC followed by their molecular characterization with the potential use not only as a new biomarker for real-time monitoring of therapy efficacy but also as a suitable tool for patient's stratification and individualization of treatment for breast cancer. Methods: A total of 54 patients with diagnosed early breast cancer were enrolled into a prospective study. Ten millilitres of peripheral blood were sequentially collected to test for the presence and characterization of CTC during the follow-up of patients. CTC isolation and detection was performed by AdnaTest BreastCancer™ (AdnaGen AG, Germany), which is based on the detection of EpCAM, HER2 and MUC1 specific transcripts in enriched CTC- lysates. cDNA from isolated CTC has been further used for newly optimized qPCR assays for breast tumor and therapy resistance associated genes: TOP1, TOP2A, CSTD, ST6GAL, KRT19 and reference gene actin. qPCR results have been analyzed by Genex software (MultiD Analysis). Results: 195 blood samples have been...

Indiana University-Purdue University Indianapolis (IUPUI) / Cancer is still among those diseases that prominently contribute to the numerous deaths that are caused each year. But as technology and research is reaching new zeniths in the present times, cure or early detection of cancer is possible. The detection of rare cells can help understand the origin of many diseases. The current study deals with one such technology that is used for the capture or effective separation of these rare cells called Lab-on-a-chip microchip technology. The isolation and capture of rare cells is a problem uniquely suited to microfluidic devices, in which geometries on the cellular length scale can be engineered and a wide range of chemical functionalizations can be implemented. The performance of such devices is primarily affected by the chemical interaction between the cell and the capture surface and the mechanics of cell-surface collision and adhesion. This study focuses on the fundamental adhesion and transport mechanisms in rare cell-capture microdevices, and explores modern device design strategies in a transport context. The biorheology and engineering parameters of cell adhesion are defined; chip geometries are reviewed. Transport at the microscale, cell-wall interactions that result in cell motion across streamlines, is discussed. We have concentrated majorly on the fluid dynamics design of the chip. A simplified description of the device would be to say that the chip is at micro scale. There are posts arranged on the chip such that the arrangement will lead to a higher capture of rare cells. Blood consisting of rare cells will be passed through the chip and the posts will pose as an obstruction so that the interception and capture efficiency of the rare cells increases. The captured cells can be observed by fluorescence microscopy. As compared to previous studies of using solid microposts, we will be incorporating a new concept of cylindrical shell micropost. This type of micropost consists of a solid inner core and the annulus area is covered with a forest of silicon nanopillars. Utilization of such a design helps in increasing the interception and capture efficiency and reducing the hydrodynamic resistance between the cells and the posts. Computational analysis is done for different designs of the posts. Drag on the microposts due to fluid flow has a great significance on the capture efficiency of the chip. Also, the arrangement of the posts is important to contributing to the increase in the interception efficiency. The effects of these parameters on the efficiency in junction with other factors have been studied and quantified. The study is concluded by discussing design strategies with a focus on leveraging the underlying transport phenomena to maximize device performance.

Проведено исследование цитотоксического действия синтезированных препаратов платины на нормальные клетки человека и различные линии опухолевых клеток. Выполнена оценка фрагментации ДНК методом электрофореза. Исследована целостность цитоплазматической мембраны клеток, подверженных действию препаратов платины. Выявлено наиболее перспективное соединение платины как возможный субстрат для разработки фармацевтических препаратов для лечения онкологических заболеваний. / Within the framework of this work, reviews of the literature on tumor cells and methods of combating malignant neoplasms, including those using platinum preparations, are collected. A study was made of the cytotoxic effect of the synthesized platinum preparations on normal human cells and various tumor cell lines. DNA fragmentation was studied by electrophoresis. A study was made of the integrity of the cytoplasmic membrane of cells exposed to platinum preparations. The most promising platinum compound has been identified as a possible substrate for the development of pharmaceutical preparations for the treatment of oncological diseases.

Este trabalho tem como principal objetivo contribuir para o desenvolvimento de novos potenciais metalofármacos de rutênio. Nele são descritas a síntese, a caracterização e a avaliação da ação antiproliferativa de alguns complexos de dirutênio (II,III) com os fármacos antiinflamatórios não-esteróides (AINEs): ibuprofeno (ibp), ácido acetilsalicílico (aas), naproxeno (npx) e indometacina (ind) e também com o ácido γ-linolênico (lin), sobre células cancerígenas. Os compostos obtidos foram caracterizados por análise elementar, espectroscopia de absorção eletrônica, medidas de susceptibilidade magnética, espectroscopia vibracional FTIR e Raman, difratometria de raios X de pó, medidas de condutividade molar e análise térmica (TG, OTAe OSC). Todos os complexos sintetizados apresentam estrutura em gaiola, com os carboxilatos derivados dos fármacos AINEs coordenados à unidade dimetálica Ru2( (II,III), em ponte equatorial, estabilizando assim a ligação direta rutênio-rutênio. As posições axiais são ocupadas por íons cloreto, no caso dos complexos [Ru2(O2(CR)4(Cl] (O2(CR = ibp, aas, npx ou ind), ou por moléculas de água, nas espécies do tipo [Ru2(O2(CR)4(H2O)2]PF6(O2CR =npx e ind). Ensaios biológicos demonstraram que os compostos [Ru2(ibp) 4Cl]•½H2O e [Ru2(npx)4(H2O)2]PF6 apresentam ação antiproliferativa sobre células de glioma de rato C6 in vitro, dependendo do tempo de exposição do meio celular ao complexo. O complexo [Ru2 (lin)4Cl] também apresenta efeito sobre a proliferação de células C6; entretanto, nesse caso, efeitos significativos são observaçlos já nas primeiras 24 h de exposição. Estudos mostraram que as bases adenina e adenosina reagem com o complexo [Ru2(OAc)4(H2O)2]PF6 sem que ocorra quebra da estrutura em gaiola. As bases nitrogenadas substituem axialmente as moléculas de água, formando pontes axiais entre duas unidades de dirutênio (II,III) no estado sólido. / The main objective of this work is to make a contribution to the development of new ruthenium metallodrugs. Synthesis, characterization and evaluation of antiproliferative action in tumor cells of some diruthenium(II,III) complexes with Nonsteroidal Anti-inflammatory Drugs (NSAIDs) such as ibuprofen, acetylsalicylic acid, naproxen, indomethacin and also γ-linolenic acid are described. The obtained compounds were characterized by elemental analysis, electronic absorption spectroscopy, magnetic susceptibility, FTIR and Raman vibrational spectroscopy, x-ray powder diffraction, molar conductivity and thermal analysis (TG, DTA and DSC). All complexes exhibit a paddlewheel structure with the NSAID carboxylates coordinated to the metal ions bridging two Ru2(II,III) dimetal units and stabilizing the ruthenium-ruthenium bound. The axial positions are occupied by chloride ions for [Ru2(O2CR)4Cl] (O2CR = ibp, aas, npx, ind), or by water molecules for [Ru4(O2CR) 4(H2O) 2]PF6(O2CR = npx, ind) complexes. Biologic assays in vitro show that antiproliferative action in C6 rat cells depends on the time of exposing the cell culture to [Ru2(ibp)4Cl]•½H2O and [Ru2 (npx)4(H2O)2]PF6 complexes. The [Ru2(1in)4Cl] compound also exhibits proliferative changes in C6 rat cells, however, significant results are observed for the first 24 hours of treatment. Some results show that adenine and adenosine bases can react with [Ru2(OAc)4(H2O)2]PF6 without breakage of the cage structure. The bases substitute the axial water molecules forming axial bridges between diruthenium units in the solid state.

Este trabalho tem como principal objetivo contribuir para o desenvolvimento de novos potenciais metalofármacos de rutênio. Nele são descritas a síntese, a caracterização e a avaliação da ação antiproliferativa de alguns complexos de dirutênio (II,III) com os fármacos antiinflamatórios não-esteróides (AINEs): ibuprofeno (ibp), ácido acetilsalicílico (aas), naproxeno (npx) e indometacina (ind) e também com o ácido γ-linolênico (lin), sobre células cancerígenas. Os compostos obtidos foram caracterizados por análise elementar, espectroscopia de absorção eletrônica, medidas de susceptibilidade magnética, espectroscopia vibracional FTIR e Raman, difratometria de raios X de pó, medidas de condutividade molar e análise térmica (TG, OTAe OSC). Todos os complexos sintetizados apresentam estrutura em gaiola, com os carboxilatos derivados dos fármacos AINEs coordenados à unidade dimetálica Ru2( (II,III), em ponte equatorial, estabilizando assim a ligação direta rutênio-rutênio. As posições axiais são ocupadas por íons cloreto, no caso dos complexos [Ru2(O2(CR)4(Cl] (O2(CR = ibp, aas, npx ou ind), ou por moléculas de água, nas espécies do tipo [Ru2(O2(CR)4(H2O)2]PF6(O2CR =npx e ind). Ensaios biológicos demonstraram que os compostos [Ru2(ibp) 4Cl]•½H2O e [Ru2(npx)4(H2O)2]PF6 apresentam ação antiproliferativa sobre células de glioma de rato C6 in vitro, dependendo do tempo de exposição do meio celular ao complexo. O complexo [Ru2 (lin)4Cl] também apresenta efeito sobre a proliferação de células C6; entretanto, nesse caso, efeitos significativos são observaçlos já nas primeiras 24 h de exposição. Estudos mostraram que as bases adenina e adenosina reagem com o complexo [Ru2(OAc)4(H2O)2]PF6 sem que ocorra quebra da estrutura em gaiola. As bases nitrogenadas substituem axialmente as moléculas de água, formando pontes axiais entre duas unidades de dirutênio (II,III) no estado sólido. / The main objective of this work is to make a contribution to the development of new ruthenium metallodrugs. Synthesis, characterization and evaluation of antiproliferative action in tumor cells of some diruthenium(II,III) complexes with Nonsteroidal Anti-inflammatory Drugs (NSAIDs) such as ibuprofen, acetylsalicylic acid, naproxen, indomethacin and also γ-linolenic acid are described. The obtained compounds were characterized by elemental analysis, electronic absorption spectroscopy, magnetic susceptibility, FTIR and Raman vibrational spectroscopy, x-ray powder diffraction, molar conductivity and thermal analysis (TG, DTA and DSC). All complexes exhibit a paddlewheel structure with the NSAID carboxylates coordinated to the metal ions bridging two Ru2(II,III) dimetal units and stabilizing the ruthenium-ruthenium bound. The axial positions are occupied by chloride ions for [Ru2(O2CR)4Cl] (O2CR = ibp, aas, npx, ind), or by water molecules for [Ru4(O2CR) 4(H2O) 2]PF6(O2CR = npx, ind) complexes. Biologic assays in vitro show that antiproliferative action in C6 rat cells depends on the time of exposing the cell culture to [Ru2(ibp)4Cl]•½H2O and [Ru2 (npx)4(H2O)2]PF6 complexes. The [Ru2(1in)4Cl] compound also exhibits proliferative changes in C6 rat cells, however, significant results are observed for the first 24 hours of treatment. Some results show that adenine and adenosine bases can react with [Ru2(OAc)4(H2O)2]PF6 without breakage of the cage structure. The bases substitute the axial water molecules forming axial bridges between diruthenium units in the solid state.

Nierenzellkarzinome (NZKs) gelten als stark immunogene Tumore. Dies ist insbesondere auf die Infiltration durch verschiedene Immunzellpopulationen, wie T-Lymphozyten und Natürliche Killer (NK)-Zellen, sowie das klinische Ansprechen auf immuntherapeutische Strategien zurückzuführen. Bisher existieren jedoch nur sehr wenige Studien zur Rolle von humanen nativen dendritischen Zellen (DCs) in NZK-Geweben und über die Tumor-vermittelte Modulation dieser DCs. DCs nehmen als professionelle Antigen-präsentierende Zellen eine zentrale Schlüsselrolle bei der Induktion und Aufrechterhaltung der angeborenen sowie adaptiven Immunantwort ein. Daher wurde im Rahmen dieser Arbeit erstmals der Effekt von klarzelligen NZKs auf den Phänotyp sowie die immunmodulatorischen Fähigkeiten von 6-sulfo LacNAc+ (slan)DCs evaluiert. SlanDCs, welche eine große Subpopulation humaner Blut-DCs darstellen, sind neben der Sekretion großer Mengen proinflammatorischer Zytokine dazu befähigt, Tumorzellen direkt zu lysieren. Des Weiteren sind slanDCs in der Lage, die antitumoralen Effekte von NK-Zellen zu fördern und CD4+ T-Helfer-Zellen sowie Tumor-reaktive CD8+ T-Lymphozyten effizient zu stimulieren. Angesichts dieser proinflammatorischen Eigenschaften können slanDCs wesentlich an einer Tumor-gerichteten Immunantwort beteiligt sein. Auf dieser Grundlage erfolgte im Rahmen der vorliegenden Arbeit der immunhistochemische Nachweis von slanDCs in klarzelligen NZK-Geweben. Im Vergleich zu Tumor-freiem Nierengewebe trat in den primären Tumorgeweben eine erhöhte Zahl infiltrierender slanDCs auf. Zudem wurde die Präsenz von slanDCs in Lymphknoten- sowie Fernmetastasen von NZK-Patienten beobachtet. Weiterführende Untersuchungen an frischen klarzelligen NZK-Geweben demonstrierten, dass NZK-infiltrierende slanDCs einen unreifen Phänotyp ausprägen und Interleukin-10 produzieren. Ausgehend von diesen Erkenntnissen erfolgten funktionelle Analysen, bei denen der Einfluss der kommerziell erhältlichen klarzelligen NZK-Linien ACHN und Caki-1 sowie der primären klarzelligen NZK-Linien MZ1257RC und MZ2877RC auf bedeutende immunmodulatorische Fähigkeiten von slanDCs untersucht wurde. In diesem Zusammenhang zeigte sich, dass NZK-Zellen effektiv in der Lage sind, sowohl die slanDC-vermittelte Proliferation von CD4+ und CD8+ T-Lymphozyten, als auch die slanDC-induzierte Differenzierung naïver CD4+ T-Lymphozyten in proinflammatorische T-Helfer 1-Zellen zu inhibieren. Darüber hinaus wurde demonstriert, dass NZK-Zellen das Potenzial von slanDCs zur Aktivierung von NK-Zellen hemmen. Untersuchungen der zugrunde liegenden Mechanismen zeigten, dass die funktionelle Inhibition von slanDCs durch klarzellige NZK-Zellen über membranständige Moleküle vermittelt wird. Die im Rahmen dieser Dissertation gewonnenen Erkenntnisse weisen darauf hin, dass NZKs die Ausreifung sowie wesentliche funktionelle Eigenschaften von DCs inhibieren. Dies deutet auf einen neuen Immunescape-Mechanismus klarzelliger NZKs hin, welcher auf einer Tumorzell-vermittelten Generierung von tolerogenen slanDCs basiert und eine unzureichende Aktivierung der angeborenen sowie adaptiven Tumor-gerichteten Immunantwort zur Folge hat. Diese neuen Erkenntnisse können einen Beitrag zu einem besseren Verständnis der Interaktion von NZKs mit nativen humanen DCs leisten und die Konzeption neuer therapeutischer Strategien ermöglichen, welche auf einer Verstärkung der antitumoralen Eigenschaften von DCs beruhen.

No description available.

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 201 pages. Includes vita. Includes bibliographical references.

Submitted by Marco Antonio Oliveira da Silva (maosilva@ipen.br) on 2016-08-25T11:05:49Z No. of bitstreams: 0 / Made available in DSpace on 2016-08-25T11:05:49Z (GMT). No. of bitstreams: 0 / A radioimunoterapia (RIT) faz uso de anticorpos monoclonais conjugados com radionuclídeos emissores α ou β-, ambos para terapia. O tratamento baseia-se na irradiação e destruição do tumor, preservando os órgãos normais quanto ao excesso de radiação. Radionuclídeos emissores β- como 90Y, 131I, 177Lu e 188Re, são úteis para o desenvolvimento de radiofármacos terapêuticos e, quando associados a AcM como o Anti-CD20 são importantes principalmente para o tratamento de Linfomas Não Hodgkins (LNH). 188Re (Eβ- = 2,12 MeV; Eγ= 155 keV; t1/2 = 16,9 h) é um radionuclídeo atrativo para RIT. O Centro de Radiofarmácia do IPEN possui um projeto que visa a produção do radiofármaco 188Re-Anti-CD20. Com isso,este estudo foi proposto para avaliar a eficácia desta técnica de marcação para tratamento em termos compartimentais e dosimétricos. O objetivo deste trabalho consistiu na compararação da marcação do AcM anti-CD20 com 188Re com a marcação do anticorpo com 90Y, 131I, 177Lu e 99mTc (pelas suas características químicas similares) e 211At, 213Bi, 223Ra e 225Ac. Através do estudo de técnicas de marcação relatadas em literatura, foi proposto um modelo compartimental para avaliação de sua farmacocinética e estudos dosimétricos, de alto interesse para a terapia. A revisão de dados publicados na literatura, possibilitou demonstrar diferentes procedimentos de marcação, rendimentos de marcação, tempo de reação, impurezas e estudos de biodistribuição. O resultado do estudo mostra uma cinética favorável para o 188Re, pelas suas características físicas e químicas frente aos demais radionuclídeos avaliados. O estudo compartimental proposto descreve o metabolismo do 188Re-anti-CD20 através de um modelo compartimental mamilar, que pela sua análise farmacocinética, realizada em comparação aos produtos marcados com emissores β-: 131I-antiCD20, 177Lu-anti-CD20, o emissor γ 99mTc-anti-CD20 e o emissor α 211At-Anti-CD20, apresentou uma constante de eliminação de aproximadamente 0,05 horas-1 no sangue do animal. A avaliação dosimétrica do 188Re-Anti-CD20 foi realizada através de duas metodologias: pelo método de Monte Carlo e pelo uso de uma fonte pontual β- através da Fórmula de Loevinger via programa Excel. Através da Fórmula de Loevinger fez-se a validação do método de Monte Carlo para a dosimetria do 188Re-Anti-CD20 e dos demais produtos. As doses e as taxas de doses obtidas pelos dois métodos foram avaliadas em comparação à dosimetria do 90Y-Anti-CD20, 131I-Anti-CD20 e do 177Lu-Anti-CD20, obtidas pela mesma metodologia. O estudo de dose foi realizado utilizando modelos matemáticos considerando um camundongo nude de 25g, simulando diferentes tamanhos de tumor e diferentes formas de distribuição do produto dentro do animal. De acordo com os resultados obtidos, pela energia de emissão β-, 188Re-Anti-CD20 apresenta maior deposição de energia para tumores volumosos em relação aos demais produtos avaliados. Em uma simulação com 100% do produto captado pelo tumor, 89% da dose total manteve-se absorvida pelo tumor, preservando a integridade de ógãos críticos como coração (2%), pulmões (5%), coluna (4%), fígado (0,014%) e rins (0,0007%). Em uma simulação onde há uma biodistribuição do produto no organismo do animal, 38% da dose total é absorvida pelo tumor e >3% é absorvida pela coluna. Nessa situação mais próxima da realidade, a extrapolação dos dados para um humano de 70kg, mostrou que a dose absorvida no tumor corresponde a cerca de 33%; na coluna 7% e o coração receberia uma dose de 35% do total. A análise compartimental e dosimétrica apresentada neste trabalho, realizada através do uso de um modelo animal para o 188Re-Anti-CD20 mostra que o produto desenvolvido e apresentado em literatura é candidato promissor para a RIT. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP