Literatura académica sobre el tema "TDM au 18F-FDG"

Les changements thérapeutiques durant la dernière décennie ont contribué à une amélioration de la survie du Myélome Multiple (MM). Cela s’est accompagné de l’utilisation de nouveaux outils d’imagerie corps-entier, tels que la TEP-TDM au 18-FDG (TEP-FDG) et l’IRM, remplaçant les radiographies standards, à des fins diagnostiques mais également d’évaluation thérapeutique. Chacune de ces modalités présente cependant ses limites. L’imagerie de diffusion en IRM, l’analyse de l’hétérogénéité tumorale aidée des techniques d’intelligence artificielle (IA) ainsi que le développement de nouveaux radiotraceurs TEP sont trois voies d’explorations importantes pouvant contribuer à une meilleure prise en charge du MM. L’objectif général de ce travail a été d’évaluer l’apport de ces nouvelles approches lors du diagnostic initial du MM ainsi que lors de l’évaluation thérapeutique. La première partie de ce travail a été de comparer prospectivement dans une population de myélomes multiples de novo la détection des lésions osseuses focales par TEP-FDG et IRM de diffusion corps-entier (DW-MRI). La deuxième partie de travail a été d’évaluer l’apport de la Radiomique couplée à pour le diagnostic de l’atteinte ostéo-médullaire diffuse en TEP-FDG. La troisième partie de ce travail a été consacré à la comparaison prospective des valeurs pronostiques de la TEP-FDG et de la DW-MRI lors de l’évaluation thérapeutique du MM éligible à une autogreffe de cellules souches hématopoïétiques (ASCT). La dernière partie décrit le protocole comparant les performances de la TEP-TDM à la 18F-Fluorocholine (FCH) à la TEP-TDM au 18-FDG dans le bilan initial du myélome multiple
Therapeutic changes over the past decade have contributed to an improvement in the survival of Multiple Myeloma (MM). Newer whole-body imaging techniques, such as 18-FDG PET-CT (PET-FDG) and MRI, have replaced radiological surveys for diagnostic purposes but also therapeutic evaluation. However, each of these modalities has its limits. Diffusion-weighted MRI (DW-MRI), analysis of tumor heterogeneity with the help of artificial intelligence (AI) as well as the development of new PET radiotracers are three important ways that may contribute to improve MM patient’s management. The general objective of this work was to assess the contribution of these new approaches during the initial diagnosis of MM as well as during therapeutic evaluation.The first part of this work was to prospectively compare the detection of focal bone lesions by FDG-PET and DW-MRI in a population of newly diagnosed MM. The second part of this work was to assess the contribution of radiomics coupled to AI for the diagnosis of diffuse bone marrow disease in FDG-PET. The third part of this work was devoted to the prospective comparison of the prognostic values of FDG-PET and DW-MRI during the therapeutic evaluation of MM eligible to autologous stem cell transplantation. The last part describes the protocol that aims at comparing the performance of 18F-Fluorocholine PET-CT and FDG-PET in the initial work-up of MM

Le but de cette thèse est d'évaluer l'utilisation de la TEP/CT avec le 18F-FDG pour l'évaluation de la fonction testiculaire et d'optimiser et de standardiser le protocole d'acquisition et l'analyse du volume testiculaire pour ce faire. Dans le chapitre I, nous donnons un aperçu de la littérature où nous établissons que l'absorption de 18F-FDG est corrélée avec la spermatogenèse en raison de la présence des transporteurs GLUT 3 sur les cellules de Sertoli et les spermatides et non sur les cellules de Leydig qui sont responsables de la stéroïdogenèse. Nous donnons ensuite un aperçu du problème de santé publique que pose la stérilité masculine en indiquant les différentes applications cliniques possibles de l'imagerie fonctionnelle des testicules. Dans le chapitre II, nous examinons la corrélation significative entre l'absorption de 18F-FDG en termes d'intensité et de volume d'absorption et la fonction testiculaire via les paramètres de l'analyse du sperme. Dans le chapitre III, nous nous concentrons sur la standardisation du protocole d'acquisition pour cette indication spécifique, après un bref aperçu technique de la TEP/TDM et de ses limites. La première étude ayant été réalisée par le biais d'un volume testiculaire délimité manuellement, nous avons ré-analysé la corrélation avec une méthode de segmentation adaptative solide et reproductible du volume dans un deuxième article. Nous nous sommes également concentrés sur l'optimisation du protocole d'acquisition en évaluant l'impact de l'activité urinaire intense sur l'absorption testiculaire. Nous avons d'abord examiné cet impact à l'aide d'études de fantômes dans lesquelles nous avons simulé la vessie et les testicules. Nous avons ensuite procédé à une étude clinique visant à évaluer et à comparer deux protocoles de diurétiques. Dans le chapitre IV, nous abordons le sujet important, et encore plus dans ce contexte andrologique, des problèmes liés à la radioprotection d'une TEP/CT avec le 18F-FDG. Enfin, dans le chapitre V, nous donnons un aperçu de certaines des questions qui restent à traiter et des perspectives futures de cette nouvelle orientation dans le domaine de la médecine nucléaire que nous pourrions appeler "andrologie nucléaire"
The aim of this thesis is to evaluate the use of PET/CT with 18F-FDG for an assessment of the testicular function and to optimise and standardise the acquisition protocol and the testicular volume analysis in order to do that. In chapter I we provide a literature overview where we establish that the 18F-FDG uptake is correlated with the spermatogenesis because of the presence of GLUT 3 transporters on the Sertoli cells and the spermatides and not on the Leydig cells which are responsible for the steroidogenesis. We then provide an overview of the public health problem of male infertility where we point out different possible clinical applications for testicular functional imaging. In chapter II we examine the significant correlation between 18F-FDG uptake in terms of intensity and volume of uptake and the testicular function via the parameters of the sperm analysis. In chapter III, we focus on the standardisation of the acquisition protocol for this specific indication, after a brief technical overview of the PET/CT and of its limitations. Because the first study was done via a manually delineated testicular volume, we re-analysed the correlation with a solid and reproducible adaptive volume segmentation method in a second article. We further focussed on optimising the acquisition protocol by evaluating the impact of the intense urinary activity on the testicular uptake. First we examined this impact with phantom studies where we simulated the bladder and the testes. We proceeded with a clinical study where we aimed to evaluate and compare 2 diuretic protocols. In chapter IV we address the overall important subject, and even more so in this andrological context, of the radioprotection related issues of a PET/CT with 18F-FDG. Finally, in chapter V we provide an overview of some of the issues still to be addressed and the future perspectives for this new direction in the field of nuclear medicine that we could name 'nuclear andrology'

Le cancer du col de l'utérus, bien que rare, est une maladie grave touchant souvent des femmes jeunes, avec environ 3 000 nouveaux cas par an en France. La survie dépend du stade de la maladie au diagnostic : les formes avancées nécessitent une radiochimiothérapie concomitante, et l'atteinte ganglionnaire lombo-aortique est un facteur pronostique essentiel. Traditionnellement, la stadification chirurgicale était utilisée pour évaluer cette atteinte, mais la TEP/TDM au 18F-FDG est aujourd’hui préférée, bien qu’elle soit limitée dans la détection de métastases de petite taille.Notre travail explore le potentiel de la radiomique, qui analyse des caractéristiques quantitatives issues de l’imagerie pour prédire des résultats cliniques, dans ce contexte. Dans un premier chapitre, nous avons développé un « modèle TEP » simple pour prédire l’atteinte lombo-aortique, basé sur le nombre d’adénopathies iliaques et les technologies time-of-flight des machines TEP plus modernes. Le second chapitre se concentre sur une revue systématique des applications de la radiomique dans les cancers du col, en évaluant la qualité méthodologique des études via le Radiomics Quality Score. Enfin, le troisième chapitre propose un modèle prédictif intégrant des caractéristiques radiomiques et cliniques, afin de prédire l’atteinte lombo-aortique occulte.Cette recherche souligne la nécessité de modèles prédictifs robustes pour améliorer la prise en charge des cancers du col, avec un potentiel de personnalisation des traitements grâce à des biomarqueurs non invasifs
Cervical cancer, though rare, is a serious disease often affecting young women, with approximately 3,000 new cases per year in France. Survival depends on the disease stage at diagnosis: advanced stages require concomitant chemoradiotherapy, and para-aortic lymph node involvement is a critical prognostic factor. Traditionally, surgical staging was used to assess this involvement, but 18F-FDG PET/CT is now preferred, although it has limitations in detecting small metastases.Our work explores the potential of radiomics, which analyzes quantitative features extracted from imaging to predict clinical outcomes, in this context. In the first chapter, we developed a simple “PET model” to predict para-aortic lymph node involvement based on the number of iliac lymph nodes and the time-of-flight technology of modern PET machines. The second chapter focuses on a systematic review of radiomics applications in cervical cancer, evaluating the methodological quality of studies using the Radiomics Quality Score. Finally, the third chapter presents a predictive model combining radiomic and clinical features to predict occult para-aortic lymph node involvement.This research highlights the need for robust predictive models to improve the management of cervical cancer, with the potential to personalize treatments through non-invasive biomarkers

L’objectif global de cette thèse était d’étudier, à partir de la cohorte des patients du centre de référence PXE du CHU d’Angers, différente aspects du phénotype cardiovasculaire (CV) du PXE. Ainsi, dans un premier travail, nous avons pu montrer dans l’étude GOCAPXE, que les calcifications ectopiques seraient un processus actif pouvant être détecté par une imagerie moléculaire utilisant un traceur spécifique de l’activité ostéoblastique, le 18-Fluorure de Sodium (18F-NaF); que ce processus était détectable avant même que ces calcifications ne soient visibles par les techniques d’imageries classiques; que ce processus était localisé aux zones habituellement lésées dans le PXE : les plis de flexion et le cou pour la peau et l’artère fémorale superficielle pour le vaisseau. Cette technique mériterait d’être validée dans une étude longitudinale et son rôle en tant biomarqueur diagnostique et de suivi serait ainsi envisageable. Le deuxième travail de cette thèse a été d’étudier les conséquences morphologiques et fonctionnelles d’une augmentation chronique de la pression artérielle chez les patients PXE. Cette question était pertinente car dans la littérature, la question d’une hypertension artérielle (HTA) chez les PXE reste controversée. Nous avons ainsi montré pour la première fois que dans un modèle d’HTA induite par le Deoxycorticostérone (DOCA)-Salt chez la souris Abcc6-/- cette augmentation de la pression artérielle induisait un remodelage CV avec à la fois de la fibrose et des calcifications dystrophiques. Les résultats de cette étude suggèrent la nécessité d’un contrôle optimal de la pression artérielle chez les patients PXE. Le troisième travail de cette thèse a été de caractériser une lésion de la carotide interne détectée avec une fréquence élevée dans la cohorte angevine. Nous avons pu montrer que cette anomalie était une hypoplasie de la carotide interne d’origine probablement congénitale. Chez les patients de la cohorte angevine, cette lésion était associée à des anévrismes intracrâniens mais nous n’avons pas retrouvé d’association avec la survenue d’accident vasculaire cérébral. Ainsi, les résultats de cette étude invitent les praticiens prenant en charge des patients PXE à la rechercher systématiquement dans le bilan vasculaire d’un patient PXE. Si une telle lésion est retrouvée, une imagerie vasculaire intracrânienne devrait être proposée à la recherche d’anévrismes et leur prise en charge discuté en concertation multidisciplinaire. Enfin, le dernier travail a permis de montrer qu’un traitement systémique par le Thiosulfate de Sodium (STS), utilisé dans la calciphylaxie rénale, était efficace sur la régression des calcifications artérielles et cutanées chez une jeune garçon ayant un phénotype CV gravissime résultant de la combinaison délétères de plusieurs gènes pathogènes du spectre PXE Ce traitement mériterait d’être validé dans un essai thérapeutique chez l’humain mais aussi la démonstration de ses mécanismes d’action dans le modèle murin Abcc6-/-. Nous suggérons d’utiliser ce traitement en cas de PXE sévère et rapidement progressif notamment sur le plan vasculaire. Au terme de ce travail de thèse, nous avons montré que le gène ABCC6 était impliqué dans le remodelage vasculaire à la fois au niveau développemental (Hypoplasie Carotidienne) mais aussi acquis (Fibrose, Calcification Cardiaque Dystrophique). Nous avons montré aussi que les calcifications dans le PXE étaient tissus et localisations spécifiques, que ces calcifications étaient actives. Enfin nous avons ouvert la porte à un traitement des formes graves du PXE avec le Thiosulfate de Sodium. Une approche thérapeutique multimodale ciblant plusieurs mécanismes concourant aux calcifications seraient judicieux à évaluer dans les futurs essais cliniques
Since the discovery of the ABCC6 gene in 2000, mutations are at the origin of PseudoxanthomeElastic (PXE), knowledge of genetics, pathophysiology, phenotypic characterizations have has mademajor advances, notably with the Discovery in 2013 of the fundamental role of Pyrophosphateinorganic (PPi) as a deficient anti‐calcifying factor in patients. The overall goal of this thesis was tostudy, from the cohort of patients at the center of PXE reference of the CHU d'Angers, differentaspects of cardiovascular phenotype (CV) of PXE. Thus, in a first work, we were able to show in thestudy GOCAPXE, that ectopic calcifications would be a active process that can be detected by imagingUsing a specific activity tracer Osteoblastic, 18‐sodium fluoride (18F‐NaF); that this process wasdetectable even before these calcifications are not visible by conventional imaging techniques; thatthis process was localized to areas usually injured in the PXE: flexion folds and neck for skin and thesuperficial femoral artery for the vessel. This technique should be validated in a study longitudinaland its role as a diagnostic biomarker In this way, monitoring and monitoring could be considered.The second work of this thesis was to study the morphological consequences and functional of achronic increase in blood pressure in PXE patients. This question was relevant because in theliterature, the question of a high blood pressure (hypertension) in PXE remains controversial. Wehave thus shown for the first time that in a model of HTA induced by the Deoxycorticosterone(DOCA)‐Salt in Abcc6‐/‐ this increase in blood pressure led to a CV remodeling with both fibrosis andcalcifications dystrophic. The results of this study suggest need for optimal control of blood pressurein patients. The third work of this thesis was to characterize a lesion of the internal carotid detectedwith high frequency in the Angevine cohort. We have could show that this abnormality washypoplasia of the Probably congenital internal carotid. In the patients of the angevine cohort, thislesion was associated with intracranial aneurysms but we have not found in association with theoccurrence of vascular accident brain. Thus, the results of this study invite practitioners supportingPXE patients to search for it systematically in the vascular balance of a PXE patient. If such a lesion isfound, vascular imaging Intracranial should be proposed to research Aneurysms and theirmanagement discussed in consultation multidisciplinary. Finally, the latest work has made it possibleto show that systemic treatment with Thiosulphate Sodium (STS), used in renal calciphylaxia, waseffective on the regression of arterial calcifications and skin in a young boy with a phenotype CVGravel resulting from the deleterious combination of several pathogenic genes of the PXE spectrumThis treatment would deserve be validated in a human therapeutic trial but also the demonstrationof its mechanisms of action in the Abcc6‐/‐murin model. We suggest using this treatment for severeand rapidly progressive PXE especially on the vascular plane.At the end of this thesis work, we showed that the ABCC6 gene was involved in vascular remodelingat both at the developmental level (Carotid Hypoplasia) but also acquired (Fibrosis, CardiacCalcification Dystrophic). We also showed that calcifications in PXE were tissues and locationsspecific, that these calcifications were active. Finally we have opened the door to a treatment ofsevere forms of PXE with Sodium Thiosulphate. An approach multimodal therapy targeting multiplemechanisms this would be useful to evaluate in future clinical trials

Antes de se iniciar os estudos clínicos de uma nova droga, é necessário realizar uma bateria de testes de segurança, para avaliar o risco humano. Os radiofármacos como qualquer outra nova droga, devem ser testados levando em conta sua especificidade, duração de tratamento e principalmente a toxicidade de ambas as partes, a molécula não marcada e a sua radioatividade em si, além das impurezas provindas da radiólise. Órgãos regulatórios como o Food and Drug Administration-EUA (FDA) e a Agência de Medicina Européia (EMEA), estabelecem guias para a regulamentação de produção e pesquisas de radiofármacos, No Brasil a produção de radiofármacos não era regulamentada até o final de 2009, quando foram estabelecidas pela Agência Nacional de Vigilância Sanitária (ANVISA) as resoluções nº 63, que visa as Boas Práticas de Fabricação de Radiofármacos e a nº 64 que visa o registro do radiofámaco. Para a obtenção do registro de radiofármacos são necessárias a comprovação da qualidade, segurança, eficácia e especificidade do medicamento. Para a segurança dos radiofármacos devem ser apresentados estudos de toxicidade aguda, subaguda e crônica como também a toxicidade reprodutiva, mutagênica e carcinogênica. Hoje o IPEN-CNEN/SP produz um dos radiofámacos mais importantes da medicina nuclear, o 18F-FDG, que é utilizado em muitas aplicações clínicas, em particular no diagnóstico e estadiamento de tumores. O objetivo deste trabalho foi avaliar a toxicidade sistêmica (aguda/subaguda) do radiofármaco 18F- FDG em um sistema teste in vivo, conforme preconiza a RDC nº 64, que servirá de modelo para os protocolos de toxicidade dos radiofármacos produzidos no IPEN. Os ensaios realizados foram: os testes de toxicidade aguda e de toxicidade subaguda, estudos de biodistribuição do 18F-FDG, ensaio cometa e toxicidade reprodutiva. Na toxicidade aguda, ratos sadios foram injetados com 18F- FDG e observados durante 14 dias enquanto na toxicidade subaguda os animais foram observados durante 28 dias. Os resultados não mostraram nenhuma evidência de toxicidade na exposição ao 18F-FDG na toxicidade aguda e na subaguda. A biodistribuição demonstrou resultados semelhantes aos da literatura, onde a bexiga é o órgão que mais recebe radiação. O ensaio cometa mostrou que a radiação do radiofármaco não foi significativa para gerar danos no DNA. Na toxicidade reprodutiva, casais de ratos expostos ao 18F-FDG geraram filhotes completamente normais e saudáveis. Por fim, o 18F-FDG não evidenciou nenhuma toxicidade.
Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN . The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected with 18F-FDG and observed for 14 days while in subacute toxicity animals were observed for 28 days. The results showed no evidence of toxicity at exposure 18F-FDG in acute and subacute toxicity. The biodistribution showed similar results to the literature, where the bladder is the organ that receives the most radiation. The comet assay showed that the radiation from the radiopharmaceutical was not significant to generate DNA damage. In reproductive toxicity in coupled rats exposed to 18F-FDG generated completely normal and healthy puppies. Finally, the 18F-FDG did not show any toxicity.

La tomographie par émission de position (TEP) est une technique d'imagerie médicale permettant de visualiser la consommation de glucose dans l'organisme après administration du fluorodésoxyglucose (FDG). Le tomodensitomètre à rayons x (TDM) couplé au détecteur TEP permet de localiser précisément les anomalies. La concentration tumorale de FDG est mesurée sur les coupes TEP à l'aide du Standardized Uptake Value (SUV) dont une mesure précise et reproductible est nécessaire pour détecter une réponse précoce à un traitement cytotoxique. Les techniques de mesures actuelles sont en deux dimensions (2D) à l'aide d'une région d'intérêt (ROI) manuelle tracée sur l'image TEP : elles sont grossières, peu reproductibles. L'objectif de ce travail était d'utiliser les données morphologiques fournies par la TDM pour délimiter automatiquement et en 3D la lésion pour le calcul du SUV. La 1ère partie présente les notions théoriques importantes permettant de mieux appréhender le sujet. La 2ème partie expose dans le détail les différentes études réalisées : après avoir décrit dans un 1er chapitre l'environnement de travail, nous avons démontré dans le 2ème que la méthode actuelle de calcul du SUV est grossière et peu productible. Dans le 3ème chapitre, une recherche de ROI 3D directement sur l'image TEP est décrite. Cette méthode testée sur 82 patients atteints de tumeur pulmonaire de forme et de complexité variées a fourni une excellente reproductibilité mais présentait l'inconvénient de ne pas utiliser toutes les données fournies par l'examen TEP-TEDM. Dans le 4ème chapitre, la recherche de ROI s'est effectuée en 3D sur l'image TDM. Cette ROI a été ensuite copiée dans l'image TEP pour le calcul des SUV. Nous avons montré dans le 5ème chapitre sur 106 patients que la reproductibilité du calcul du SUV était améliorée lorsqu'un seuillage était appliquédans l'image TEP après la recopie de la ROI TDM. Enfin, nous avons terminé notre travail en montrant, sur un suivi de 23 patients, que la méthode présentée permettait d'évaluer de façon précise l'influence d'une thérapie sur une tumeur. En effet, chez ces 23 patients, le SUVmax, le SUVmoy etla taille des ROI sont respectivement passés de 13,8±8,9, 6,8±3,7 et 634±872 lors de l'examen initial à 7,9±5,3, 4,0±2,2 et 396±573 lors du second examen (p<0,01 pour les 3 paramètres). En conclusion, l'utilisation des données de la TDM permet d'améliorer la reconductibilité des mesures de SUV en TEP-TDM au FDG.

No Brasil e no mundo a medicina nuclear vem ganhando destaque com as técnicas diagnósticas que permitem o estudo metabólico de doenças, alterando significativamente o gerenciamento dos pacientes. Essa tecnologia inovadora vem trazendo expectativas tanto para os setores especializados como para a sociedade. Nesse trabalho foi estudada a utilização do radiofármaco 18F-FDG na região metropolitana de São Paulo e nas áreas adjacentes, bem como a estrutura do mercado atual e das dificuldades a serem superadas com o aumento da demanda do 18F-FDG. A pesquisa contou com uma análise do mercado de radiofármacos internacional e das principais alterações que vem ocorrendo nessa área no Brasil nos últimos anos. Foram realizadas entrevistas com profissionais atuantes na área de medicina nuclear e coleta de dados através de questionário enviado para os centros consumidores do radiofármaco na região coberta pela pesquisa. As entrevistas expressaram as opiniões dos entrevistados sobre as transformações nesse setor e as tendências futuras e os dados coletados no questionário serviram de complementação a utilização do radiofármaco nos equipamentos do tipo Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET) e Positron Emission Tomography / Computer Tomography (PET/CT). O maior uso do 18F-FDG tem sido para o diagnóstico oncológico nos equipamentos do tipo PET e PET/CT. Essa utilização deverá crescer nos próximos anos, podendo se expandir para outras especialidades como neurologia e cardiologia. Apesar de restrita atualmente as cidades de São Paulo e Rio de Janeiro deverá haver uma expansão dessa modalidade diagnóstica nos outros Estados do país que começam a estruturar produção do radioisótopo. A recente alteração na constituição que permite a produção e comercialização de radioisótopos de meia-vida curta também deverá aumentar o interesse da iniciativa privada nesse mercado, que internacionalmente possui projeções otimistas de crescimento. Existe também uma expectativa que a aprovação dos planos de saúde para a cobertura dos exames utilizando 18F-FDG no PET impulsione esse mercado ainda mais, repetindo a experiência internacional. Os recentes investimentos realizados pelo IPEN para aumentar a produção do 18F-FDG deverá garantir a oferta com confiabilidade, para a região Sudeste e Sul do país.
Nuclear Medicine in Brazil and worldwide has developed distinction with diagnosis techniques that allow metabolic research of the disease, changing in a significant fashion the patients outcome. This innovative technology leads expectations from specific fields up to society itself. This research studied the use of 18F-FDG radiopharmaceutical in the metropolitan region of São Paulo and adjacent areas, as well as the recent trade structure and the difficulties that should be overcome with the increase of the 18F-FDG demand. This research counted on the analysis of the international radiopharmaceutical trade and the main changes that have been happening in this area in Brazil during the past few years. Interviews were performed with professionals within the area of nuclear medicine and data has been collected through questionnaire sent to the consuming centers of the radiopharmaceutical in the region covered in this research. The interviews expressed the opinions of the interviewees concerning transformations in this field and future tendencies and the information obtained from the survey was the basis of complementation of the use of radiopharmaceutical on equipments such as Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET) and Positron Emission Tomography / Computer Tomography (PET/CT). The major use of 18F-FDG has been used for oncology diagnosis with equipments such as PET and PEC/CT. This use shall grow in the next years, maybe expanding to other specialties such as neurology and cardiology. Although nowadays restricted to the cities of São Paulo and Rio de Janeiro, there is a possibility of expansion to other diagnosis modalities in other states of the country that are starting to structure the production of the radioisotope. The recent change in the constitution permitting the production and commerce of short half-life radioisotopes also contributes to the increase the interest of private funding of this sector in which internationally holds optimistic projections of increase. There is also the expectancy that approving health care plans coverage of these exams using 18F-FDG with PET to boast more this sector, repeating international experience. Recent investments made by IPEN to increase the production of 18F-FDG shall guarantee the offer of confidentiality for the Southeast and Southern regions of the country.

O sistema microPET/CT é um importante equipamento utilizado nas pesquisas de imagem diagnóstica em pequenos animais. O radiofármaco mais usado nesta tecnologia é o fluordeoxiglicose marcado com flúor-18. Este estudo tem como objetivo efetuar o controle radiológico no laboratório de pesquisa microPET/CT do Centro de Radiofarmácia do IPEN-CNEN/SP, de forma a satisfazer tanto as normas nacionais como as recomendações internacionais. O laboratório está classificado pela equipe de radioproteção da instalação como área supervisionada, nas quais embora não seja obrigatória a adoção de medidas específicas de proteção e segurança, devem ser submetidas reavaliações regulares das condições do ambiente de trabalho. Visando assegurar a proteção radiológica dos trabalhadores diretamente envolvidos no manuseio do equipamento, realizou-se o monitoramento do local de trabalho e a avaliação do controle de dose individual. Inicialmente foi feito o monitoramento pré-operacional, isto é, o levantamento radiométrico no laboratório. Além disso, mediu-se nível de radiação externa nas instalações do laboratório e suas adjacências, por meio da colocação de nove dosímetros termoluminescentes (TL) de CaSO4:Dy, em locais previamente selecionados. Os indivíduos ocupacionalmente expostos foram avaliados mensalmente por meio do uso de dosímetros TL posicionados no tórax e por medidas de corpo inteiro, tomadas a cada seis meses. O período do estudo foi de dois anos, com início em abril de 2014. Para o controle do microPET/CT realizou-se testes de desempenho de acordo com o protocolo padrão do equipamento e em conformidade com a norma desenvolvida pela força tarefa para estudos com PET em animais Animal PET Standard Task Force. O presente estudo permitiu demonstrar que os níveis de radiação das áreas (estimativas de dose ambiente e dose efetiva), assim como a blindagem do equipamento estão adequados de acordo com os limites da exposição ocupacional. Ressalta-se a importância de se seguir rigorosamente os princípios de radioproteção, já que se trata de pesquisas com fontes radioativas não seladas.
Micro PET/CT scanner is an essential tool generally used for small animal molecular imaging. Fluorine-18-labeled fluorodeoxyglucose is the most widely used radioisotope in this technique. The present study aimed to evaluate the radiation levels in a micro PET/CT research laboratory of the Radiopharmacy Center at IPEN-CNEN / SP, in order to accomplish both national standards and international recommendations. The radioprotection team has classified the laboratory as supervised area; even this laboratory does not require the adoption of specific measures for protection and safety, should be done regular re-evaluation of the conditions of occupational exposures. Workplace monitoring and individual control assessment were carried out to ensure the radiological protection of all workers directly involved in handling the scanner. Initially, there was conducted a radiometric survey, as well as measurements of the external radiation level in the workplace and its surroundings. To achieve this goal, there were placed nine thermoluminescent dosimeters of CaSO4:Dy in preselected locations. Monthly evaluations of the occupationally exposed individuals were carried out through the use of TL dosimeters, ported in the workers´ chest. Moreover, whole body measurements were performed every six months. The study period was about two-years which started in April 2014. All tests to evaluate micro PET/CT performance were based on the standard protocol of the equipment in accordance with the standard developed by the Animal PET Standard Task Force. Present study\'s results demonstrated that the ambient radiation levels (ambient and effective estimated radiation dose), as well as the effective shielding equipment are both adequate. This study emphasizes that it is essential to strictly follow the principles of radioprotection in workplace, whenever researches involve radioactive unsealed sources.

As doenças cardiovasculares são a principal causa de mortalidade no mundo. A aterosclerose é a base fisiopatológica dessas doenças, sendo definida como um processo crônico-inflamatório multifatorial, resultando da interação de diferentes células como linfócitos, macrófagos, células endoteliais e células musculares lisas na parede arterial. A lipoproteína de baixa densidade eletronegativa [LDL(-)], uma subfração modificada da LDL nativa, desempenha um papel-chave na aterosclerose, uma vez que as modificações sofridas por esta partícula são capazes de induzir o acúmulo de ésteres de colesterol em macrófagos e a subsequente formação de células espumosas. O sistema imunológico é crucial no processo aterogênico e estratégias terapêuticas direcionadas à imunoregulação deste processo têm sido utilizadas como novas alternativas tanto na prevenção do desenvolvimento quanto da progressão desta doença. Dentre essas estratégias, destaca-se o uso de fragmentos de anticorpos como o scFv (do inglês, single chain fragment variable), que podem ainda estar conjugados a nanopartículas com o intuito de aumentar sua eficiência de ação no organismo. Diante do papel da LDL(-) na aterosclerose, este projeto objetivou avaliar os efeitos in vitro e in vivo de um sistema nanoestruturado contendo fragmentos scFv anti-LDL(-) derivatizados na superfície de nanocápsulas sobre macrófagos murinos e humanos primários e em camundongos knockout para o gene do receptor da LDL (Ldlr-/-) no desenvolvimento e na progressão dessa doença. Demonstrou-se que o tratamento de macrófagos com a formulação scFv anti-LDL(-)-MCMN-Zn diminuiu de forma significativa a captação de LDL(-), assim como a expressão de IL-1β (mRNA e proteína) e MCP-1 (mRNA). Foi demonstrada a internalização da nanoformulação pelos macrófagos via diferentes mecanismos de endocitose, demonstrando seu potencial uso como carreador de fármacos. In vivo, a nanoformulação diminuiu de forma significativa a área da lesão aterosclerótica em camundongos Ldlr-/- submetidos à avaliação pela técnica de tomografia por emissão de pósitrons (do inglês, PET), utilizando o radiotraçador 18F-FDG (18F-desoxiglicose), associada à tomografia computadorizada (CT) com agente de contraste iodado, além da análise morfométrica das lesões no arco aórtico. O conjunto dos resultados obtidos evidenciou a ação ateroprotetora da formulação scFv anti-LDL(-)-MCMN-Zn, reforçando seu potencial como estratégia terapêutica na aterosclerose.
Cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerosis is the pathophysiological basis of these diseases, defined as a chronic inflammatory multifactorial process, resulting from the interaction of several cells such as lymphocytes macrophages, endothelial cells and smooth muscle cells within the arterial wall. The electronegative low-density lipoprotein [LDL(-)], a modified subfraction of native LDL, plays a key role in atherosclerosis, since its modifications are capable of inducing the accumulation of cholesteryl esters in macrophages and the subsequent foam cells formation. The immune system is crucial in atherogenic process and therapeutic strategies directed to the immunoregulation of this process have been used as a new alternative in the prevention of the development as well as the progression of this disease. Among these strategies, it is the use of antibody fragments such as scFv (single chain fragment variable), which may be also conjugated to nanoparticles in order to increase their efficiency in the body. Given the role of LDL(-) in atherosclerosis, the aim of this project was to evaluate the in vitro and in vivo effects of a nanostructured system containing scFv anti-LDL(-) fragments derivatized on the surface of nanocapsules on murine and human primary macrophages and in the development and progression of the disease in LDL receptor knockout mice (Ldlr-/-). It was demonstrated that the treatment of macrophages with scFv anti-LDL(-)-MCMN-Zn formulation significantly decreases the uptake of LDL(-) and the expression IL-1β (mRNA and protein) and MCP-1 (mRNA). Moreover, the internalization of the nanoformulation by macrophages through different endocytosis mechanisms was shown, demonstrating its potential use as a nanocarrier. In vivo, the nanoformulation decreased the area of atherosclerotic lesions in Ldlr-/- mice evaluated by positron emission tomography with 18F-FDG associated with computed tomography with iodinated contrast agent (PET/CT), besides the lesion morphometric analysis at the aortic arch Thus, these data provide evidence of the atheroprotection action of the ateroprotection action of the scFv anti-LDL(-)-MCMN-Zn formulation, suggesting its promising use as a therapeutic strategy for atherosclerosis.

L’imagerie scintigraphique des cancers thyroïdiens différenciés (CTD) présente la particularité d’utiliser deux radiopharmaceutiques, l’iode 131 (131I) et le 18-Fluorodésoxyglucose (18FDG). La fixation de ces traceurs dépend habituellement du degré de différenciation et de l’agressivité de la tumeur. L’objectif de ce travail était d’étudier l’apport de différents aspects techniques et d’instrumentation, à savoir l’imagerie hybride par TEMP/TDM et TEP/TDM, la point-spread function (PSF), la taille des voxels et la technologie TEP digitale, et d’explorer si d’autres traceurs TEP pouvaient présenter un intérêt. Le but de la première partie était d’étudier les performances de la TEP/TDM au 18FDG à l’étage cervical pour la détection de la maladie ganglionnaire. Une acquisition TEP/TDM dédiée a amélioré la détection de la maladie tumorale par rapport à l’acquisition classique. L’utilisation de la PSF a permis de détecter des tailles de lésions plus petites et la durée optimale de cette acquisition a été évaluée. Des reconstructions avec des tailles de voxels ultra-fines ont été réalisées sur TEP digitale pour étudier l’impact de la PSF et des voxels ultra-fins sur les données quantitatives. La seconde partie a porté sur l’imagerie 131I-TEMP/TDM et 18FDG-TEP/TDM, afin de quantifier le volume de la maladie persistante. Il a ainsi été montré que la masse tumorale était corrélée au risque post-opératoire et avait un impact sur la réponse au traitement. L’objectif de la troisième partie était d’étudier un autre traceur TEP, la 18-Fluorocholine (FCH), ainsi qu’un marqueur de la néovascularisation, l’antigène membranaire spécifique de la prostate (PSMA). Nos données suggèrent qu’un examen TEP à la FCH négatif au sein d’un nodule thyroïdien à cytologie indéterminée permettrait d’éliminer la malignité, et pourrait éviter des chirurgies inutiles. Par ailleurs, le marquage au PSMA évalué par immunohistochimie dans les néo-vaisseaux est associé à des facteurs de mauvais pronostic. D’autres études sont nécessaires pour confirmer l’intérêt éventuel des examens TEP à la FCH et au 68Ga-PSMA en oncologie thyroïdienne
Radioiodine (131I) and 18-Fluorodeoxyglucose (18FDG) are two radiopharmaceuticals used for scintigraphic imaging in differentiated thyroid cancers (DTC). Tumour uptake of each tracer depends on tumour differentiation and aggressiveness. Our goal was to further assess various technical aspects in DTC imaging workup, such as SPECT/CT and PET/CT, point-spread function (PSF), voxel size, digital PET, and to explore further other PET tracers. The aim of the first part was to assess the performance of 18FDG PET/CT for the detection of neck lymph node involvement. A dedicated PET/CT acquisition improved tumour detection compared to the whole-body acquisition. PSF reconstruction allowed detection of smaller cancer deposits and the optimal acquisition duration time was assessed. Using digital PET acquisitions, ultra-thin voxels reconstructions were performed. The impact of ultra-thin voxels and PSF on quantitative values was evaluated. The second part focused on 131I-SPECT/CT and 18FDG-PET/CT imaging, in an attempt to assess tumour burden of persistent disease. Tumor burden was correlated with the postoperative risk and affected the response to therapy. In the third part, another PET tracer, i.e. 18-Fluorocholine (FCH), and a marker of neovasculature, i.e. prostate-specific membrane antigen (PSMA), were studied. FCH PET/CT offered high negative predictive value to reliably exclude cancer in PET-negative nodules with indeterminate cytology and might prevent unnecessary surgeries. Also, PSMA expression assessed with immunohistochemistry was associated with poor prognosis factors. Further studies are needed to confirm new insights of FCH PET and 68Ga-PSMA PET in DTC

O uso de equipamentos híbridos tem trazido aumento das doses recebidas por pacientes de diagnostico em PET/CT. Existem atualmente várias metodologias dosimétricas, dificultando o estabelecimento de níveis de referências. Esse trabalho visa estimar as doses absorvidas e efetivas em exames oncológicos de PET/CT, comparando diferentes metodologias. Utilizou-se os fatores de dose publicados pela ICRP 106 para exames de 18F-FDG para a dosimetria PET; e para dosimetria do exame de CT foram comparadas três metodologias: software ImPACT, dosimetria termoluminescente (TLD) com simulador Alderson e metodologia recomendada pela AAPM nº96. As doses dos exames PET e CT foram somadas para obter a dose total do exame de PET/CT. Para dosimetria do PET os órgãos com maior dose absorvida foram a bexiga, o cérebro e coração. Para dose absorvida no CT as maiores diferenças foram para a pele, cérebro, tireoide e bexiga, sendo os órgãos críticos a tireoide e a pele. Apenas a metodologia da AAPM nº96 subestima a dose efetiva do CT quando comparada com a medida por TLD. Para o PET/CT, verificou-se que os órgãos críticos apresentam valores consideráveis de dose equivalente, recomendando a otimização dos protocolos e avaliação de risco. O presente estudo demonstrou que a simulação pelo ImPACT é o método dosimétrico que mais se aproxima da medida experimental realizada com TLD. Observa-se, ainda, a importância de investigar as doses equivalentes em órgãos ao invés de apenas as doses efetivas, como muitas vezes tem sido reportado na literatura.