Este trabalho consiste na síntese e na caracterização de complexos inéditos de gálio, índio, cobalto, cobre e molibdênio.Baseando-se na potencial aplicação na terapia dos complexos de gálio e índio, dois novos complexos, um de gálio e um de índio, foram sintetizados utilizando como ligante o ânion monovalente da 2,3-dihidroxipiridina e um de gálio foi sintetizado utilizando como ligante o mono ânion da 2-hidroxipiridina-N-óxido. Um ligante macrocíclico derivado do cyclam foi sintetizado. Posteriormente, foi preparado um complexo de cobre e um de cobalto com o macrociclo, visando a potencial aplicação de complexos desse tipo na medicina nuclear. Cinco complexos de molibdênio foram sintetizados, sendo dois utilizando ligantes hidrazonas e três com ligantes ditiocarbazatos, visando sua potencial aplicação na terapia da doença de Chagas. Os compostos foram caracterizados por espectroscopia de absorção na região do infravermelho, análise elementar (C, H, N e S), espectroscopia de ressonância magnética nuclear (1H e no caso do ligante macrociclo 13C), espectrometria de massas (MS-ESI) e difração de raios X.Após completa caracterização, os complexos de gálio e índio tiveram sua atividade antitumoral in vitro avaliada em linhagens de células derivadas de tumores e, como estudo pioneiro, os complexos também tiveram sua atividade tripanocida avaliada, assim como os complexos de molibdênio. / This work consists on the synthesis and characterization of novel complexes of gallium, indium, cobalt, copper and molybdenum.Based on the potential therapeutic application of gallium and indium complexes, two new complexes with the monovalent anion of 2,3-dihydroxypyridine were synthesized, one of gallium and one of indium. In addition, one gallium complex was prepared with the mono anion of 2-hydroxypyridine N-oxide as ligand. A cyclam derivative macrocycle ligand was synthesized. Subsequently, a copper and a cobalt complex were synthesized with the new macrocycle, aiming their potential application in nuclear medicine. Five molybdenum complexes were synthesized, two with hydrazones and three with dithiocarbazates as ligands, focusing their potential application in Chagas disease therapy. The compounds were characterized by infrared absorption spectroscopy, elemental analysis (C, H, N and O), nuclear magnetic resonance (1H and, in the case of the macrocycle ligand, 13C), mass spectrometry (ESI-MS), and single crystal X-ray diffraction. After complete characterization, the complexes of gallium and indium had their in vitro antitumor activity assessed front tumor-derived cell lines and as a first study the complexes were also evaluated regarding their trypanocidal activity, as well as the molybdenum complexes.

Introdução: Postula-se que a creatina (ácido-metil-guanadino-acético), descrita como um \"tampão energético\" dos processos metabólicos cerebrais, poderia melhorar o desempenho cognitivo nos indivíduos em desenvolvimento. Objetivo: Investigar os efeitos da suplementação com creatina na função cognitiva e nas concentrações cerebrais em crianças saudáveis. Métodos: O presente ensaio-clínico, duplo-cego, randomizado e controlado por placebo, foi composto por 67 crianças saudáveis com idades entre 10 e 12 anos (11,5 ± 0,8). Os participantes receberam 0,3g/Kg/dia de creatina monohidratada (n= 35) ou dextrose (n=32). No período basal, e após sete dias de intervenção, os participantes foram submetidos à bateria de testes cognitivos. Em uma sub amostra aleatória de participantes (creatina: n = 11 e placebo: n = 10), as concentrações cerebrais de creatina foram avaliadas no córtex pré-frontal dorsolateral esquerdo, hipocampo esquerdo e lobo occipital, pela técnica de espectroscopia por ressonância magnética (1H-ERM). Resultados: Os escores obtidos nos testes de função executiva e aprendizagem verbal não foram estaticamente diferentes entre os grupos antes ou após a intervenção (p > 0,05). As concentrações cerebrais de creatina (expresso em mmol/L) não foram estaticamente diferentes entre os grupos no córtex pré-frontal dorsolateral esquerdo (creatina - pré: 6,9 ± 0,8, pós: 6,7 ± 0,5; placebo - pré: 6,7 ± 0,8; pós: 6,9 ± 0,09; p = 0,50), hipocampo esquerdo (creatina - pré: 7,0 ± 0,5, pós: 6,8 ± 0,7; placebo - pré: 6,7 ± 1,0; pós: 6,6 ± 1,9; p = 0,80), e no lobo occipital (creatina - pré: 7,9 ± 0,9, pós: 8,1 ± 0,8; placebo - pré: 7,7 ± 0,4; pós: 7,8 ± 0,5; p = 0,70). Conclusão: o protocolo de suplementação de creatina por sete dias mostrou-se incapaz de provocar aumento nas concentrações cerebrais de creatina ou no desempenho cognitivo em crianças. Esses dados sugerem que essa população depende principalmente da síntese cerebral do que a creatina exógena para manter a homeostase desse nutriente no cérebro / Background: It has been hypothesized that creatine (?-methyl-guanidine-acetic acid), which is thought to energetically buffer brain metabolic processes, could enhance cognitive performance in developing individuals. Aims: This study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine concentration in healthy youth. Methods: This was a 7-day, double-blind, randomized, placebo-controlled study. The sample comprised 67 healthy children aged 10 to 12 years. The participants were given either creatine supplementation ((0.3 g/Kg/day; n = 35) or 2) placebo (dextrose; n = 32). At baseline and after 7 days of intervention, participant undertook a battery of cognitive tests. In a random sub-sample of participants (creatine: n = 11 and placebo: n = 10), brain creatine concentration was also assessed in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe, by proton magnetic resonance spectroscopy (1H-MRS) technique. Results: As a result, scores obtained from Rey Auditory Learning Test, Stroop Test, Trail Making Test, and Raven Progressive Matrices did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine concentration (expressed in mmol/L) was not significantly different between groups in left dorsolateral prefrontal cortex (creatine - pre: 6.9 ± 0.8, post: 6.7 ± 0.5; placebo - pre: 6.7 ± 0.8; post: 6.9 ± 0.09; p = 0.50), left hippocampus (creatine - pre: 7.0 ± 0.5, post: 6.8 ± 0.7; placebo - pre: 6.7 ± 1.0; post: 6.6 ± 1.9; p = 0.80), and occipital lobe (creatine - pre: 7.9 ± 0.9, post: 8.1 ± 0.8; placebo - pre: 7.7 ± 0.4; post: 7.8 ± 0.5; p = 0.70). Conclusion: In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine concentration or cognitive performance in healthy youth, suggesting that this population mainly rely in brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis

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.

Esta tese apresenta a síntese e a caracterização de novos complexos de rênio e tecnécio utilizando como agentes complexantes ligantes assimétricos do tipo base de Schiff e ligantes triaminas derivadas da dietilenotriamina. Os ligantes assimétricos foram sintetizados através de reações de condensação entre 2,2\'-dihidroxibenzofenona e as aminas alifáticas etilenodiamina e dietilenotriamina, formando, respectivamente, os ligantes 2,2\'-(((2-aminoetill)imino)metileno)difenol(HL1) e 2,2\'-(((2-((2-aminoetil)amino)etil)imino) metileno)difenol (HL2). Os ligantes simétricos foram sintetizados através de reações de condensação entre benzaldeído, 4-hidroxibenzofenona e 3- e 4-metoxibenzaldeído com a amina alifática dietilenotriamina, formando, respectivamente, os ligantes simétricos tridentados tricloridrato de N1-benzil-N2-(2-(benzilamino)etil)etano-1,2-diamina (HL3), 4,4\'-(((azanodiilbis(etano-2,1-diil))bis- (azanediil))bis(phenilmetileno))difenol (HL4), tricloridrato de N1-(4-metoxibenzil)-N2-(2-((4-metoxibenzil)amino)etil) etano-1,2-diamina (HL5) e tricloridrato de N1-(3-metoxibenzil)-N2-(2-((3-metoxibenzil)amino)etil)etano-1,2-diamina (HL6). Reações de complexação foram conduzidas com os precursores metálicos de ReI eTcI. O complexo [Re(CO)5Br] foi utilizado como precursor de ReI. Foi obtido o complexo neutro do tipo fac-[Re(CO)3(L1)] e complexos catiônicos do tipo fac-[Re(CO)3(HL2,3,4,5,6)]Br. Os ligantes e complexos foram caracterizados por ponto de fusão, análise elementar (CHN), espectroscopia de absorção na região do infravermelho, espectroscopia de absorção na região do ultravioleta visível, espectroscopia de ressonância magnética nuclear de 1H e 13C, espectrometria de massas (MS-ESI) e, no caso dos complexos com os ligantes HL1,2,5,6, difração de raios X pelo método do monocristal. Foi realizada a marcação do ligante HL3 com o complexo fac-[[99mTc](H2O)(CO)3]+, formando o complexo fac-[[99mTc](CO)3(HL3)]Br e outras espécies em solução, que foram separadas por HPLC. Adicionalmente, realizou-se um estudo comparativo entre o método convencional de síntese (aquecimento) com o método de síntese no qual microondas são utilizadas. O complexo de tecnécio foi caracterizado por HPLC e eletroforese em papel. Foram realizados testes de estabilidade em cisteína, histidina e tampão PBS. Os testes de estabilidade mostraram que o complexo apresenta boa estabilidade por período de 3 horas. Foi determinado o coeficiente de partição desse complexo, tendo sido observado o caráter lipofílico do mesmo. Foram também realizados testes biológicos in vitro de captação e extrusão com células B16F10 (melanoma murino), onde as células captaram o complexo fac-[[99mTc](CO)3(HL3)]Br,em torno de 4,2%, e mantiveram retidas em seu interior cerca de 20% do complexo, após 60 minutos de incubação. O teste de viabilidade celular por azul de Tripan, mostrou estabilidade das células, durante os experimentos de captação e extrusão, frente às espécies radioativas, apresentando uma viabilidade celular superior a 90% em todos os casos. / This thesis presents the synthesis and characterization of novel rhenium and technetium complexes using as complexing agents asymmetric ligands (Schiff\'s bases type ligands) and triamines ligands derived from diethylenetriamine. The asymmetric ligands were synthesized by condensation reactions between 2,2\'-dihydroxybenzophenone and the aliphatic amines ethylenediamine and diethylenetriamine, giving rise, respectively, to the ligands 2,2\'-(((2-aminoetill)imino) methylene)diphenol (HL1) and 2,2\'-(((2-((2-aminoethyl)amino)ethyl)imino) methylene) diphenol (HL2). The symmetrical ligands were synthesized by condensation reactions between benzaldehyde, 4-hydroxybenzophenone and 3- and 4-methoxybenzaldehyde with the aliphatic amine diethylenetriamine, resulting in the formation, respectively, of the symmetrical tridentated ligands trihydrochloride N1-benzyl-N2-(2-(benzylamino)ethyl)ethane-1,2-diamine (HL3), 4,4\'-(((azanodiilbis(ethane-2,1-diyl))bis(azanediil))bis(phenilmetileno))diphenol (HL4), trihydrochloride N1-(4-methoxybenzyl)-N2-(2-((4-methoxybenzyl)amino)ethyl)ethane-1,2-diamine (HL5) and trihydrochloride N1-(3-methoxybenzyl)-N2-(2-((3-methoxybenzyl)amino)ethyl)ethane-1,2-diamine (HL6). Complexation reactions were carried out using ReI and TcI as metal precursors. The complex [Re(CO)5Br] was used as ReI precursor. Neutral complexe of the type fac-[Re(CO)3(L1)] and cationic complexes of the type fac-[Re(CO)3(HL2,3,4,5,6)]Br were obtained. The ligands and complexes were characterized by melting point, elemental analysis (CHN), infrared absorption spectroscopy, UV-visible absorption spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry (MS-ESI) and for the complexes with the ligands HL1,2,5,6, single crystal X ray diffraction method. Labeling studies were carried out for the HL3 ligand with the complex fac-[[99mTc](H2O)(CO)3]+, forming the complex fac-[[99mTc](CO)3(HL3)]Br and other species in solution, which were separated by high performance liquid chromatography (HPLC). Additionally, a comparative study was done between the conventional (heating) and the synthesis method using microwaves. The technetium complex was characterized by HPLC and electrophoresis on paper. Stability tests were conducted on cysteine, histidine and PBS buffer. The stability tests showed that the compound presents good stability over a 3 hour period. The lipophilic character of the complex was confirmed by the determination of the partition coefficient. In addition, In vitro biolgical tests of captation and influx were performed on B16F10 cells (murine melanoma). The cells captured around 4.2% of the complex fac-[[99mTc](CO)3(HL3)]Br and retained 20% of the amount inside after 60 minutes of incubation. The Trypan blue exclusion test of cell viability showed stability of the cells during the influx and captation experiments, front of the radioactive species, showing cell viability greater than 90% in all cases.

Este estudo foi desenvolvido no Instituto de Pesquisas Energéticas e Nucleares - IPEN mais especificamente, no Centro de Radiofarmácia - CR que realiza pesquisa e processamento de radiosótopos como o 99Mo, 131I, 123I, 67Ga, 201Tl, 18F, 177Lu e 153Sm para uso em medicina nuclear. Os radioisótopos são produzidos em escala industrial e a instalação foi projetada para atender aos padrões de segurança radiológica e às exigências da Garantia de qualidade. No CR há profissionais qualificados que realizam as tarefas de manutenção dos equipamentos e instrumentos, instalados nas celas de processamento de radiofármacos, sem os quais não é possível conduzir a produção com segurança e qualidade. Neste estudo foi realizada uma pesquisa denominada Pesquisa de Variáveis, baseada nas operações de manutenções e intervenções em áreas restritas do CR e no levantamento da distribuição de doses nessas tarefas no período de 2005 a 2011. Esta pesquisa tem por objetivo identificar e determinar as principais variáveis que tem impacto sobre a dose do trabalhador. Os resultados obtidos foram apresentados para variável Indivíduo Ocupacionalmente Exposto - IOE, variável Operação, variável Área/Cela, variável Tipo de Tarefa e variável Duração de Operação, em função da variável Dose. O objetivo deste trabalho foi contribuir com melhorias nas operações em áreas restritas que possam resultar em doses individuais mais baixas sem causar alterações significativas na rotina de trabalho. A análise dos resultados mostrou que a Pesquisa a Variáveis identificou os fatores que mais impactam com a dose recebida. São eles variável Operação, variável Área/Cela e variável Tipo de Tarefa. / This study was developed at IPEN - Institute of Energy and Nuclear Research more specifically in CR - Center of Radiopharmacy that conducts research and processing of radiopharmaceuticals such as 99Mo, 131I, 123I, 67Ga, 201Tl, 18F, 177Lu and 153Sm for use in nuclear medicine. The radioisotopes are produced on industrial scale and the facility was designed to meet the standards of radiation safety requirements and quality control. To ensure the production, there are qualified professionals who perform the maintenance tasks of the equipments and instruments, in the radiopharmaceuticals processing cells, to conduct the work with quality and safety. This study were based in a research called \"Search of Variables\", for the operations carried out in restricted areas of CR, taking into account the doses distribution data for these tasks, from 2005 to 2011. This research aims to identify and determine the key variables that impact on the worker\'s dose. The results were presented for the following variables: Individual occupationally exposed - IOE, operation variable, Area/Cell, Type of Task and Duration of Operation, which depend on the variable Dose. The main objective is to contribute to the improvements in operations in restricted areas that may result in lower individual doses without causing significant changes in the working routine. The results have shown the variable that most affect the dose of the workers, which are: the variable Operation, the variable Area/Cell and the variable Type of Task.

Bakgrund: Utvecklingen av genomlysnings-baserade interventioner har varit framgångsrika de senaste årtiondena, då det gäller behandling av patienter. Införandet av genomlysning har dock medfört risker, för både patient och personal. Detta på grund av att stråldoser ökat i takt med en större efterfrågan på genomlysning och en utveckling av mer avancerade undersökningar. Med tanke på att stråldosen från intervention har en biologisk långtidseffekt, så är strålskydd ett upp-märksammat och återkommande ämne då det påverkar både sjukvårdspersonal, patienter och sam-hället. Brist på strålskydd och oaktsamhet hos operatörerna medför en ökad risk för strålningsindu-cerade skador. Eftersom antalet interventioner ständigt ökar så behövs även en ökad medvetenhet hos vårdpersonal kring vilka risker strålningen kan medföra och hur de kan undvikas. Syfte: Att beskriva vilka åtgärder som kan vidtas för att minska stråldosen för personal och patient vid angiografi/intervention. Metod: En systematisk litteraturstudie har använts. Resultat: I det sammanställda resultatet har flera olika strålskyddsåtgärder presenterats för att reducera stråldosen under intervention/angiografi. Genomlysningstid, modern teknik, uppdaterade inställningar i apparaturen och blyskydd har alla visat sig minska stråldosen markant till patient och personal. Utbildning och feedback ses även vara en viktig del i strålskyddsarbetet då det utgör grun-den för att riktlinjer kring strålskydd följs. Slutsats: Att det finns alternativa strålskyddsåtgärder vid IR- undersökningar/åtgärder är något som kan konstateras. Faktum är att en kombination av dessa åtgärder helt klart vore optimalt, för ökad säkerhet hos både personal och patienter vid exponering av strålning. / Background: The development of fluoroscopy-guided interventions the recent decades has resulted in a successful treatment of patients. However, the introduction of these diagnostic devices carry risks for both patients and staff. This is due to the fact that radiation doses increases in line with a greater demand for interventions and the development of advanced procedures. The radiation may cause long-term biological effects which makes radiation protection an important subject as it affects both staff, patients and society. Lack of radiation protection and negligence among operators cause an increased risk of radiation-induced damage. As the number of interventions constantly increase, improved knowledge is needed. Aim: The aim of this study is to describe which methods can be applied in order to reduce radiation doses for staff and patients in angiography / intervention. Method: A systematic study of existing literature. Results: The result shows several different radiation protection strategies to reduce the radiation dose during intervention / angiography. Fluoroscopy time, modern technology, updated settings in the device and lead protection have all been shown to reduce radiation dose significantly to both patients and staff. Education and feedback are also considered to be an important part of the radiation safety as they provide the basic guidelines on radiation protection. Conclusion: There is a lot of alternative radiation protection strategies in fluoroscopy-guided inter-ventions. In fact, a combination of these strategies would clearly be optimal for increased safety for both staff and patients exposed to radiation.

El ciprofloxacino marcado con tecnecio-99m (99mTc-ciprofloxacino) es un radiofármaco cuyo interés radica en el diagnóstico y control terapéutico de las infecciones. El marcaje de este antibiótico ya se ha llevado a cabo por diferentes grupos de investigación pero es necesario el desarrollo de nuevos métodos de preparación y control de calidad para obtener un radiofármaco lo más puro posible así como para evaluar la acumulación in vitro en bacterias. Este radiofármaco debe cumplir los requisitos más estrictos de pureza y calidad si se pretende su aplicación en la práctica clínica y poder competir con las pruebas ya existentes en el campo de la infección. Para el marcaje, en este trabajo se ha usado ciprofloxacino clorhidrato, ácido clorhídrico, cloruro de estaño, ácido tartárico, agua inyectable, cloruro sódico 0,9% y tecnecio. El control de calidad se ha basado en cromatografía en capa fina combinando dos de sílica gel y una en fase reversa. El estudio del marcaje propuesto para el radiofármaco muestra una clara influencia de la concentración de ácido tartárico durante la reacción mostrándose un equilibrio entre 99mTc-ciprofloxacino y 99mTc-tartrato. Usando una relación molar ciprofloxacino / ácido tartárico de 50 a 100, el producto mayoritario es el esperado (99mTc-ciprofloxacino). En cambio, con relaciones molares ciprofloxacino / ácido tartárico menores de 10 se obtienen grandes cantidades de 99mTc-tartrato. Sin embargo, a medida que disminuimos la concentración de ácido tartárico aumenta la proporción de especies coloidales, las cuales son impurezas a evitar en esta exploración diagnóstica, debido a la posibilidad de falsos positivos. La acumulación in vitro en bacterias se llevó a cabo mediante dos cepas (con y sin mecanismos de resistencia) de Staphylococcus aureus y Pseudomonas aeruginosa a los 5 y 30 minutos. La evaluación de la acumulación de tecnecio libre se realizó para demostrar si toda la señal radiactiva intracelular era debida al antibiótico marcado. El 99mTc-ciprofloxacino se acumuló por igual en todas las cepas bacterianas estudiadas mientras que el tecnecio libre (99mTcO4-) no mostró acumulación. El estudio clínico se realizó en 40 pacientes con sospecha clínica y/o analítica de aflojamiento séptico en prótesis osteoarticulares de cadera, rodilla y hombro. La adquisición de imágenes consistió en una gammagrafía ósea convencional y en la combinación de una gammagrafía con leucocitos marcados con 99mTc-HMPAO y una gammagrafía medular (99mTc-coloide). La prueba con 99mTc-ciprofloxacino se realizó a las 1, 4 y 24 horas post inyección intravenosa de 370MBq. El diagnóstico final de infección de prótesis osteoarticular se estableció cuando en 2 cultivos de tejido periprotésico de 6 sean positivos para el mismo microorganismo o haya evidencia macroscópica de material purulento. De los 40 pacientes incluidos en el estudio se documentó infección en 16 correspondientes a las prótesis en 8 caderas, 6 rodillas y 2 hombros. De los microorganismos aislados, 9 fueron resistentes a ciprofloxacino. En los 24 casos restantes se excluyó el diagnóstico de infección. Los mejores resultados de la gammagrafía con 99mTc-ciprofloxacino en pacientes se obtienen en las imágenes a las 24 horas, con una sensibilidad del 88%, una especificidad del 71%, un valor predictivo positivo del 67% y un valor predictivo negativo del 89%. La gammagrafía con 99mTc-ciprofloxacino puede ser una alternativa útil a la gammagrafía con leucocitos marcados en la evaluación de la sospecha de infección de prótesis de cadera. La especificidad encontrada no es adecuada para recomendarla en el diagnóstico de infección en prótesis de rodilla. / 99mTc-ciprofloxacin is a radiopharmaceutical used in the detection of osteoarticular prosthesis infection. In this work, a labelling procedure using tin(II) chloride and L-tartaric acid instead of tin(II) tartrate is reported. Quality control is based on thin layer chromatography. Intracellular accumulation of the labelled antibiotic and free pertechnetate (99mTcO4-) in bacteria was also analyzed. Finally, a clinical trial was performed. The study of the influence of tartaric acid concentration during the labelling reaction showed the existence of an equilibrium between 99mTc-ciprofloxacin and 99mTc-tartrate. When using a molar ratio ciprofloxacin/tartaric acid from 50 to 100, 99mTc-ciprofloxacin is the main product. Significant amounts of 99mTc-tartrate were observed when the ciprofloxacin/tartrate ratio is minus or equal than 10 and it can become the main compound at lower values. Radiocolloid quantity becomes important at high ratio values. The study of the intracellular accumulation of ciprofloxacin, 99mTc-ciprofloxacin and 99mTcO4- was performed in Staphylococcus aureus and Pseudomonas aeruginosa strains with and without the presence of an efflux pump as a mechanism of resistance. Accumulation of 99mTcO4- was performed to ensure that the entire radioactivity signal was due to the 99mTc-ciprofloxacin. Also, the accumulation of non-labelled ciprofloxacin was done to ensure that the strains were able to pump out the antibiotic. 99mTc-ciprofloxacin accumulated equally intracellularly in all the strains tested while 99mTcO4- did not show accumulation. Forty patients (26 women, 14 men) with local pain in the hip (21), knee (16), or shoulder (3) prosthesis were recruited. 99mTc-ciprofloxacin scintigraphy was performed at 1, 4, and 24h after intravenous injection of 370MBq. A routine bone scan, 99mTc-HMPAO leukocyte scan and 99mTc-colloid scan were performed. Diagnosis of arthroplasty infection was established in 16 out 40 cases: 8 hips, 6 knees, 1 shoulder. From the isolated microorganisms, 9 were resistant to ciprofloxacin. 99mTc-ciprofloxacin scintigraphy showed the 24h image to be the best acquisition time-point. The sensitivity, specificity, negative predictive value and positive predictive value at 24h were 88, 71, 67, and 89%. 99mTc-ciprofloxacin scintigraphy can be a useful alternative in the diagnosis of arthroplasty infection of the hip. The lack of specificity of makes this technique inadequate for knee prostheses.

<p>Positron emission tomography (PET) is a nuclear medicine diagnostic imaging exam of metabolic processes in the body. Radiotracers, which consist of positron emitting radioisotopes and a molecular probe, are introduced into the body, emitted radiation is detected, and tomographic images are reconstructed. The primary clinical PET application is in oncology using a glucose analogue radiotracer, which is avidly taken up by some cancers.</p><p>It is well known that PET performance and image quality degrade as body size increases, and epidemiological studies over the past two decades show that the adult US population's body size has increased dramatically and continues to increase. Larger patients have more attenuating material that increases the number of emitted photons that are scattered or absorbed within the body. Thus, for a fixed amount of injected radioactivity and acquisition duration, the number of measured true coincidence events will decrease, and the background fractions will increase. Another size-related factor, independent of attenuation, is the volume throughout which the measured coincidence counts are distributed: for a fixed acquisition duration, as the body size increases, the counts are distributed over a larger area. This is true for both a fixed amount of radioactivity, where the concentration decreases as size increases, and a fixed concentration, where the amount radioactivity increases with size.</p><p>Time-of-flight (TOF) PET is a recently commercialized technology that allows the localization, with a certain degree of error, of a positron annihilation using timing differences in the detection of coincidence photons. Both heuristic and analytical evaluations predict that TOF PET will have improved performance and image quality compared to non-TOF PET, and this improvement increases as body size increases. The goal of this dissertation is to parameterize the image quality improvement of TOF PET compared to non-TOF PET as a function of body size. Currently, no standard for comparison exists.</p><p>Previous evaluations of TOF PET's improvement have been made with either computer-simulated data or acquired data using a few discrete phantom sizes. A phantom that represents a range of attenuating dimensions, that can have a varying radioactivity distribution, and that can have radioactive inserts positioned throughout its volume would facilitate characterizing PET system performance and image quality as a function of body size. A fillable, tapered phantom, was designed, simulated, and constructed. The phantom has an oval cross-section ranging from 38.5 &times; 49.5 cm to 6.8 &times; 17.8 cm, a length of 51.1 cm, a mass of 6 kg (empty), a mass of 42 kg (water filled), and 1.25-cm acrylic walls.</p><p>For this dissertation research, PET image quality was measured using multiple, small spheres with diameters near the spatial resolution of clinical whole-body PET systems. Measurements made on a small sphere, which typically include a small number of image voxels, are susceptible to fluctuations over the few voxels, so using multiple spheres improves the statistical power of the measurements that, in turn, reduces the influence of these fluctuations. These spheres were arranged in an array and mounted throughout the tapered phantom's volume to objectively measure image quality as a function of body size. Image quality is measured by placing regions of interest on images and calculating contrast recovery, background variability, and signal to noise ratio.</p><p>Image quality as a function of body size was parameterized for TOF compared to non-TOF PET using 46 1.0-cm spheres positioned in six different body sizes in a fillable, tapered phantom. When the TOF and non-TOF PET images were reconstructed for matched contrast, the square of the ratio of the images' signal-to-noise ratios for TOF to non-TOF PET was plotted as a function, <italic>f</italic>(<italic>D</italic>), of the radioactivity distribution size, <italic>D</italic>, in cm. A linear regression was fit to the data: <italic>f</italic>(<italic>D</italic>) = 0.108<italic>D</italic> - 1.36. This was compared to the ratio of <italic>D</italic> and the localization error, <italic>&sigma;_d</italic>, based on the system timing resolution, which is approximately 650 ps for the TOF PET system used for this research. With the image quality metrics used in this work, the ratio of TOF to non-TOF PET fits well to a linear relationship and is parallel to <italic>D/&sigma;_d</italic>. For <italic>D</italic> < 20 cm, there is no image quality improvement, but for radioactivity distributions <italic>D</italic> > 20 cm, TOF PET improves image quality over non-TOF PET. PET imaging's clinical use has increased over the past decade, and TOF PET's image quality improvement for large patients makes TOF an important new technology because the occurrence of obesity in the US adult population continues to increase.</p> / Dissertation

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1. INTRODUCTION Lung cancer is the most common malignancy in the world and accounts for 1.09 million new cases with 972 000 deaths per year. In Lithuania too, lung cancer is the most commonly diagnosed cancer in men with nearly 1500 new cases each year. Lung cancer is five times more common in men than in women. At present, most patients who receive an initial diagnosis of lung cancer have advanced stage disease (stage IV – 30.2%), making cure with currently available therapies unlikely. The main prognostic information with regard to survival is associated with the biological characteristics of the primary tumour (histological subtype, aggressiveness, differentiation, etc.), the extent of spread to regional or distant lymph nodes or to the other structures, and the operability of the patient (age, function of residual lung, co-morbidity). Because the outcome is associated with the histological subtype and stage of the lung cancer at the diagnosis, there has been persistent interest in designing and testing various radiological methods for early detection of lung cancer. Chest radiography, computed tomography (CT), magnetic resonance imaging (MRI) can not only identify specific features in lung nodules, but add important information about the localisation, size and extent of the primary tumour (T), detect invasion of major mediastinal structures and chest wall, and locoregional (N) and distal spread of the tumour. Although theoretically features such as nodal shape... [to full text]