La synthèse de nouveaux radiotraceurs permettant un diagnostic précoce de la maladie d'Alzheimer par imagerie par tomographie de Positron (TEP) est en plein essor. Des dérivés d'inositols, ayant montré des propriétés d'agrégation vis-à-vis des plaques amyloïdes, ont été choisis comme plateforme, afin de concevoir et de synthétiser de nouveaux traceurs pour cette maladie. Quatre générations de radiotraceurs ont été conçues. La première génération est le scyllo-inisitol dont un des hydroxyles est remplacé par un fluor-18. Les secondes et troisièmes générations correspondent à des inositols de configuration myo et scyllo sur lesquels est accroché un bras-espaceur carboné de 1 à 3 atomes de carbone portant le fluor-18. Ceci permettra de conserver la structure de l'inositol. La dernière génération correspond à un inositol sur lequel le bras carboné portant le fluor est additionné par création d'un lien de type éther. La synthèse de cette famille de molécules permet ainsi d'obtenir un bras plus long. / The synthesis of new radiotracers to diagnose earlier Alzheimer's disease by Positron Emission Tomography (PET) is a rapidly growing field. Inisitol derivatives, which show aggregative properties to amyloid plaques, have been chosen as scaffold to create and synthesize new radiolabelled compounds for a early diagnostic. Four types of radiotracers have been designed. The first one is the scyllo-inositol in which one hydroxyl group is replaced by a fluorine-18. The second and third generations are inositols in myo and scyllo configurations where the fluorine-18 atom is carried by an alkyl chain. The structure of inositols is then preserved. Finally for the last generation, the alkyl chain bearing the fluorine-18 is introduced via an ether linkage. The synthesis of this type of molecules allows the incorporation of a longer spacer.

The Institute of Radiochemistry (IRC) is one of the seven institutes of the Helmholtz-Zentrum Dresden-Rossendorf (HZDR). The research activities are fully integrated into the “Nuclear Safety Research Program” of the Helmholtz Association and focused on the topic “Safety of Nuclear Waste Disposal”. The research objectives are to generate better process understanding and data for the long-term safety analysis of a nuclear waste disposal in the deep geological underground. A better knowledge about the dominating processes essential for radionuclide (actinide) mobilization and immobilization on the molecular level is needed for the assessment of the macroscopic processes which determine the transport and distribution of radioactivity in the environment. Special emphasis is put on the biological mediated transport of long-lived radionuclides in the geosphere and their interaction with different biosystems like biota and human organism for a better calculation of environmental and health risks. Advanced knowledge is needed for description of the processes dominating at the interfaces between geo- and bio-systems related to the distribution of long-lived radionuclides in various bio-systems along the food chain.

Les transporteurs d’acides aminés sont très souvent surexprimés au niveau des cellules tumorales et représentent une cible moléculaire privilégiée pour l’imagerie TEP (Tomographie par Emission de Positons) des cancers. Dans le but d’accéder à des radiotraceurs spécifiques de ces transporteurs, les travaux de thèse ont consisté à mettre au point - dans une première partie, une nouvelle méthode de marquage au fluor-18 d’acides aminés fluorés basée sur la déoxyradiofluoration de précurseurs hydroxyaminoesters, via un intermédiaire aziridinium, - et dans une seconde partie, le marquage au carbone-11 de la sulfasalazine, un inhibiteur sélectif des transporteurs Xc-. La réaction de déoxyradiofluoration des hydroxyaminoesters de structure sérine, méthylsérine ou hydroxyphénylalanine, facilement accessibles et stables, a permis d’obtenir à température ambiante les [18F]fluoroaminoesters correspondants avec efficacité et reproductibilité. La régiosélectivité de la réaction a été trouvée dépendante des substituants du cycle aziridinium et de la fonction amine. La radiosynthèse de la [11C]-sulfasalazine a été réalisée avec succès par couplage d’un sel de diazonium approprié avec l’acide [11C]salicylique obtenu par réaction de [11C]carboxylation d’un précurseur bismagnésien issu du iodophénol. L’automatisation de cette radiosynthèse est en cours d’optimisation afin de produire la [11C]sulfasalazine en quantité suffisante pour réaliser les études in vivo. / Aminoacid transporters are often overexpressed in tumour cells and they represent molecular targets of choice for cancer imaging by Positron Emission Tomography (PET). In order to access to specific radiotracers of these transporters, the thesis project aimed at developing – in a first part, a new 18F-radiolabeling method of fluoroaminoacids based on deoxyradiofluorination of hydroxyaminoester precursors via an aziridinium intermediate – and in a second part, the radiolabelling with carbon-11 of sulfasalazine, an selective inhibiter of Xc- transporters. Deoxyradiofluorination reaction of stable and easily accessible hydroxyaminoesters possessing a serine, methylserine or hydroxyphenylalanine moiety, led to [18F]fluoroaminoesters at room temperature in high and reproducible radiochemical yields. Regioselectivity was function of the substituents on aziridinium ring and amine function. The radiosynthesis of [11C]sulfasalazine has been successfully achieved by coupling reaction of an appropriate diazonium salt with [11C]salicylic acid, obtained by [11C]carboxylation of a bismagnesium precursor from iodophenol. The automation of the radiosynthesis is in progress to produce [11C]sulfasalazine for in vivo studies.

Le motif fluoropyridine est très fréquent dans les molécules d’intérêt thérapeutique et diagnostique pour l’imagerie par tomographie par émission de positons. Bien que les 3/5-[18F]fluoropyridines soient a priori plus stables in vivo que leurs analogues radiofluorés en position 2, 4 ou 6, leur radiosynthèse par voie nucléophile à partir du [18F]fluorure reste difficile et peu documentée. Dans ce contexte, les travaux ont porté sur l’étude du radiomarquage au fluor-18 de 3/5-fluoropyridines par radiofluoration de précurseurs iodoniums. Dans une première partie, la préparation d’une vingtaine de sels de iodonium possédant une structure pyridine ou pyridinium différemment substituée, a été mise au point. Une seconde partie a été dédiée à l’optimisation de la réaction de radiofluoration des sels de iodoniums. Cette étude a conduit à la mise en évidence du rôle important du TEMPO et de la base K2CO3 dans cette réaction. Enfin, la dernière partie a été consacrée à la radiosynthèse de 3/5-[18F]fluoropyridines portant des groupements carboxamides ou aminés par une approche multi-étape. L’ensemble des résultats ont montré que la radiofluoration de triflates de iodonium en présence de TEMPO était une méthode efficace, générale et robuste de radiosynthèse de 3/5-[18F]fluoropyridines. Cette méthode a été transposée avec succès sur deux automates de synthèse. / The fluoropyridinyl moieties have become of increasing importance in the development of drug candidates as well as of radiotracers for positron emission tomography (PET) imaging after radiolabeling with fluorine-18. Although 3/5-[18F]fluoropyridines are more stable in vivo than their 2,4 or 6 radiofluorinated analogues, their radiosynthesis by nucleophilic pathway from cyclotron produced [18F]fluoride remains difficult and poorly documented. In this context, the work focused on the development of a robust and general route to 3/5-[18F]fluoropyridines based on the radiofluorination of iodonium precursors. In a first part, the preparation of about twenty iodonium salts containing a pyridine or pyridinium scaffold, has been developed. A second part was devoted to the optimization of the radiofluorination reaction of iodonium salts. This study highlighted the important role of TEMPO and K2CO3 in this reaction. Finally, the last part was dedicated to the radiosynthesis of 3/5-[18F]fluoropyridines bearing carboxamide or amine groups according to a multistep approach. All the results showed that radiofluorination of iodonium triflates in the presence of TEMPO was an efficient, general and robust method for the radiosynthesis of 3/5-[18F]fluoropyridines. This method was also successfully transposed on two automated systems.

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd3+)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd3+, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of introducing high CA doses in practice in order to afford sufficient contrast. Lanthanide (Ln3+) chelates based on 1,4,7,10–tetraazacyclododecane–1,4,7,10–tetraacetate (DOTA) have been shown to be particularly stable and effective. Chelates of DOTA exist in two interconverting coordination geometries which have varying water exchange rates. Researchers have envisioned a way to increase the per-dose efficacy both by control of the Gd3+–inner–sphere water exchange rate and via binding specificity (i.e. to tumors). The efficacy gains using these approaches have thus far been modest. A thorough structural characterization of europium (Eu3+) chelates of a DOTA-derivative which cannot undergo conformational exchange was carried out. These studies show that a single enantiomer of the ligand (S)–2–(4-nitrobenzyl)–1,4,7,10–tetraazacyclododecane–1,4,7,10–tetra(α–methyl)acetate (NB–DOTMA) can yield chelates which are both diastereoisomeric (previously reported) and regioisomeric (not previously speculated). Molecular mechanics simulations generated from the characterization data indicate that the nitrobenzyl (NB) substituent is oriented in different directions for the two possible regioisomers. The NB group can be chemically converted to confer macromolecular binding capability, and the orientation of the NB substituent may have a significant impact on the binding and/or relaxation behavior of a prototypical CA. The nuclear magnetic resonance (NMR) spectra of Eu–NB–DOTMA at various temperatures were compared. Unexpectedly, the chelates showed time-averaged structures which differ with a change in water exchange rate — the faster the rate, the greater the deviation from the expected structure. Consideration of the structures of Ln3+ chelates without accounting for their dynamic behavior does not yield an accurate value for the time-averaged hydration state. These observations suggest the "optimal" water exchange rate calculated using Solomon-Bloembergen-Morgan (SBM) theory may not lead to the highest-efficacy CAs. Binding and relaxometric studies of macromolecule-targeting derivatives of Gd–NB–DOTMA both by the author and in another lab showed that the coordination isomer with the slower water exchange rate should lead to more effective contrast, in direct opposition to the prevailing view of water exchange in the MRI community. Preliminary data do not indicate that regioisomeric chelates have significantly different relaxivity or macromolecular binding behavior. The ratios between regioisomeric Ln–NB–DOTMA chelates formed were shown to be dependent on the concentration and pH of the chelation reaction, but conditions were not found which led to the production of a single regioisomer. Attempts to carry out an efficient synthesis of a Ln3+ chelate with no potential for regioisomerism were unsuccessful.

Les travaux de thèse ont porté sur le développement de deux plateformes de radiomarquage polyvalentes pour faciliter l’incorporation du fluor-18, un isotope de choix pour l’imagerie TEP (Tomographie par Emission de Positons). La première plateforme comporte une structure sultone conduisant à un [18F]fluorosulfonate par ouverture du cycle avec le [18F]fluorure. Celle-ci a été valorisée par le couplage avec des ligands 2-nitroimidazoliques pour former un agent d’imagerie TEP spécifique de l’hypoxie. Une série de dérivés caractérisés par des propriétés d’hydrophilie différentes a été synthétisée afin de comparer leur efficacité en imagerie. Parmi ces dérivés, le [18F]FLUSONIM a révélé dans différents modèles précliniques tumoraux (rhabdomyosarcome, tumeurs cérébrales et mélanome) des ratios tumeur sur bruit de fond inégalés jusqu’à présent, et ce à des temps très précoces post-injection. La deuxième plateforme est de nature boratrane. Celle-ci est capable de réagir avec le [18F]fluorure en milieu physiologique pour former un [18F]monofluoroborate zwitterionique facile à séparer du précurseur boratrane. / This work focused on the development of versatile platforms for fluorine-18 labelling. The first platform contained a sultone moiety which was converted to [18F]fluorosulfonate by ring opening with [18F]fluoride. The sultone was coupled to 2-nitroimidazolyl ligands to obtain radiotracers for hypoxia PET imaging. A series of compounds were synthesized in order to compare their performance in PET imaging. Among them, [18F]FLUSONIM displayed high tumor/background ratios after a short delay post-injection on different animal models (rabdomyosarcoma, glioblastoma and melanoma). The second platform was based on a boratrane structure, that was able to captur [18F]fluoride in aqueous medium to form zwiterionic [18F]monofluoroborate.

Em cumprimento às normas que regulam a transferência e deposição final de rejeitos radioativos, o inventário de radionuclídeos de cada embalado contendo tais rejeitos deve ser estimado e declarado. Os limites autorizados são definidos em função das doses de radiação que indivíduos do público podem vir a receber anualmente a partir do repositório. Tais limites se referem principalmente às concentrações de atividade, dadas em Bq/g, dos radionuclídeos presentes nos embalados com rejeitos. A grande maioria dos radionuclídeos emissores de raios-gama pode ter a respectiva concentração de atividade determinada diretamente por medidas externas aos embalados. Entretanto, determinação análoga para os radionuclídeos emissores exclusivos de partículas alfa ou beta, bem como de alguns emissores de raios-gama e/ou raios-X cuja energia, intensidade absoluta de emissão e/ou atividade são muito baixas denominados genericamente Radionuclídeos de Difícil Medição (RDMs) requer procedimentos radioquímicos complexos para isolar a espécie química de interesse dos interferentes presentes nas matrizes de rejeitos. Ademais, nesse caso é necessário coletar amostras de cada embalado, acarretando elevadas doses de radiação para os operadores e altos custos logísticos, decorrentes do grande número de embalados com rejeitos radioativos que necessitam de caracterização em uma instalação nuclear. Uma metodologia alternativa para abordar esse problema consiste em obter correlações empíricas entre alguns radionuclídeos possíveis de serem medidos diretamente, como 60Co e 137Cs denominados Radionuclídeos Chave (RCs) e os RDMs. Essa metodologia, denominada Fator de Escala, foi aplicada no presente trabalho com a finalidade de determinar tais correlações, na forma de Fatores de Escala ou Funções de Correlação, para os principais rejeitos de baixa e média atividades do reator nuclear de pesquisa IEA-R1. / Regulations regarding transfer and final disposal of radioactive waste require that the inventory of radionuclides for each container enclosing such waste must be estimated and declared. The regulatory limits are established as a function of the annual radiation doses that members of the public could be exposed to from the radioactive waste repository, which mainly depend on the activity concentration of radionuclides, given in Bq/g, found in each waste container. Most of the radionuclides that emit gamma-rays can have their activity concentrations determined straightforwardly by measurements carried out externally to the containers. However, radionuclides that emit exclusively alpha or beta particles, as well as gamma-rays or X-rays with low energy and low absolute emission intensity, or whose activity is very low among the radioactive waste, are generically designated as Difficult to Measure Nuclides (DTMs). The activity concentrations of these DTMs are determined by means of complex radiochemical procedures that involve isolating the chemical species being studied from the interference in the waste matrix. Moreover, samples must be collected from each container in order to perform the analyses inherent to the radiochemical procedures, which exposes operators to high levels of radiation and is very costly because of the large number of radioactive waste containers that need to be characterized at a nuclear facility. An alternative methodology to approach this problem consists in obtaining empirical correlations between some radionuclides that can be measured directly such as 60Co and 137Cs, therefore designated as Key Nuclides (KNs) and the DTMs. This methodology, denominated Scaling Factor, was applied in the scope of the present work in order to obtain Scaling Factors or Correlation Functions for the most important radioactive wastes with low and intermediate-activity level from the IEA-R1 nuclear research reactor.

O consumo de tabaco é uma das principais causas de doenças e morte prematuras no mundo; é a segunda droga mais consumida entre os adolescentes brasileiros, sendo considerado uma importante porta de entrada para o uso de drogas ilícitas. O Brasil é o segundo produtor mundial de tabaco e desde de 1993 destaca-se como o maior exportador. Os radionuclídeos naturais das séries do 232Th e 238U são encontrados no tabaco em baixas concentrações absorvidos diretamente do solo ou por deposição foliar. No ato de fumar ocorre a transferência desses radionuclídeos através da queima do tabaco para os tecidos e órgãos humanos podendo gerar lesões cancerígenas, sendo o mais relevante o câncer de pulmão. Existem poucos dados sobre a caracterização radiológica e elementar dos derivados do tabaco brasileiros, o que torna relevante o presente estudo que teve como objetivos a determinação da radioatividade natural e da concentração de elementos maiores e traços em derivados de tabaco produzidos e comercializados no Brasil. As técnicas analíticas empregadas foram alfa e beta total após separação radioquímica para os radionuclídeos 226Ra, 228Ra e 210Pb com determinação em detector proporcional de fluxo gasoso e baixa radiação de fundo, espectrometria alfa após separação radioquímica para o radionuclídeo 210Po, análise por ativação com nêutrons instrumental (INAA) e fluorescência por dispersão de raios X (EDXRF) para determinação de 238U, 232Th, elementos maiores e traços. Foram analisados produtos derivados da Nicotina tabacum L. de diferentes marcas adquiridas em tabacarias: cigarro não aromatizados, cigarro aromatizado, charuto, rapé, cigarro de palha e fumo de corda. Pela técnica de INAA foi possível determinar a concentração de 19 elementos e pela técnica de EDXRF de 31 elementos o que possibilitou uma ampla caracterização multielementar e as técnicas analíticas empregadas se mostraram complementares. Os elementos que apresentaram maiores valores de concentração foram o Ca e o K entre todas as amostras amostragem e entre todos os radionuclídeos naturais determinados o 228Ra apresentou maiores valores de concentração de atividade. A partir da concentração de atividade determinada foram calculadas a dose anual estimada e a dose anual efetiva para os radionuclídeos 210Pb e 210Po, levando-se em consideração um consumo anual de 3,65 kg de tabaco por ano. A dose anual efetiva variou de 69,5 μSv ano-1 à 121 μSv ano-1. Os produtos que apresentaram maiores valores de concentração e consequentemente maiores valores de dose anual efetiva, para a maioria dos radionuclídeos analisados, foram os cigarros de palha e fumos de corda. / Tobacco use is one of the leading causes of premature illness and death in the world; is the second most consumed drug among Brazilian adolescents, being considered an important gateway to the use of illicit drugs. Brazil is the second largest tobacco producer in the world and since 1993 it has been the largest exporter. The natural radionuclides from the 232Th and 238U series are found in tobacco at low concentrations absorbed directly from the soil or by foliar deposition. In the act of smoking occurs the transference of these radionuclides through the burning of the tobacco to the human tissues and organs and they can generate carcinogenic lesions, being the lung cancer the most relevant. There are few data on the elemental and radiological characterization of Brazilian tobacco products, which makes relevant the present study that had as objectives the determination of the natural radioactivity and the concentration of major and trace elements in tobacco products produced and marketed in Brazil. The analytical techniques employed were gross alpha and beta, after radiochemical separation for the radionuclides 226Ra, 228Ra and 210Pb with determination in a gaseous flow proportional detector of low background radiation, alpha spectrometry after radiochemical separation for the radionuclide 210Po, instrumental neutron activation analysis (INAA) and X-ray scattering fluorescence (EDXRF) for determination of 238U, 232Th, major and trace elements. Nicotine tabacum L. products from different brands acquired in cigar stores were analyzed: non-flavored cigarettes, flavored cigarettes, cigar, snuff, straw cigarettes and rope smoke. Using the INAA technique, it was possible to determine the concentration of 19 elements and with the EDXRF technique 31 elements, which enabled a wide multielementar characterization; the analytical techniques employed were complementary. The elements that presented the highest concentration values were Ca and K among all the samples and among all the natural radionuclides determined the 228Ra presented higher values of activity concentration. The estimated annual dose and annual effective dose for the 210Pb and 210Po radionuclides were calculated from the determined activity concentration, taking into account an annual consumption of 3.65 kg of tobacco per year. The effective annual dose ranged from 69.5 μSv y-1 to 121 μSv y-1. The products with the highest concentration values and hence the highest annual effective dose for the majority of the radionuclides analyzed were straw cigarettes and rope smoke.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O uso de plantas para a cura de males é um conhecimento milenar, sendo constituinte importante para a formação das bases da medicina atual. Atualmente 25% de todas as drogas mais prescritas no mudo advêm de plantas e o mercado chega a dois bilhões de dólares. As pesquisas na área de produtos naturais dependem da integração de diversas áreas, sendo, portanto multidisciplinar. As principais áreas envolvidas são a botânica, a química, farmacologia incluindo a toxicologia, bem como o emprego de avançadas técnicas analíticas. Em decorrência dessa integração surgiu a análise elementar em plantas como alvo de pesquisas pelo mundo, já que muitos desses elementos químicos participam dos constituintes ativos responsáveis pelas propriedades curativas. Estes constituintes ativos, em sua maior parte advêm do metabolismo secundário das plantas e são chamados de metabólitos secundários. Assim buscar relações entre a composição química elementar e os produtos de metabolismo secundário é etapa fundamental na compreensão das ações terapêuticas e curativas das plantas. Neste contexto a planta Talinum patens da família portulacaceae é utilizada pela cultura popular no tratamento de feridas e cortes, problemas gastrintestinais, edemas, coceiras, fadigas e cansaço mental. As folhas são utilizadas como hortaliças em alimentação humana. Com o objetivo de contribuir na elucidação das relações entre composição química elementar e metabólitos secundários da planta Talinum patens, realizou-se prospecção fitoquímica e análise por ativação neutrônica instrumental de amostras in-natura e amostras de extratos preparados com solventes de polaridade crescente. Os resultados mostraram tendência de concentração de certos elementos químicos em determinados extratos em detrimento de outros, evidenciando que a composição química elementar encontra-se interagida ou ligada a diferentes moléculas extraídas. Foi possível ainda avaliar as contribuições nutricionais das formas populares de uso e os resultados sugerem estudos epidemiológicos. / The use of plants for many diseases treatment is a millenary knowledge. These are the great importance for the formation of actual medicine bases. Actually, more than 25 % of the all drugs prescribed in the world are obtained from plants. The medicinal plants and other vegetable materials market reach to around two billions dollars. The researches of natural products depend on different scientific areas integration, therefore with multidisciplinary aspects. The mainly areas involved in these researches are botany, chemistry, pharmacology, and toxicology. In all cases are necessary the use of advanced analytical techniques. From the integration of these different areas appears the use of elemental analysis to determine the presence of some inorganic elements other than hydrogen, carbon and oxygen in plants. This analyze became a target of many researches because chemical elements are components of biologically active compounds, including those with curative properties. The bigger part of these active compounds, called secondary metabolites, is derived from the secondary plant metabolism. Than, search relations between chemical element composition and secondary metabolites represents fundamental step to understand the therapeutic actions of curative plants. Inserted in these context, Talinum patens of the Portulacaceae family is popularly used by the Patos de Minas peoples, for the cuts and wounds treatment, gastrointestinal problems, edemas, body and mental fatigue. The leaves of this plant are used in salads in human nutrition. To contribute for the relationships between elemental composition and secondary metabolites, the T. patens was submitted to phytochemical and elemental analyses. The phytochemical studies employed extraction methods using solvent of different polarity as well as chromatographic techniques. For the elemental analyses was used instrumental neutron activation analysis (INAA). The results showed a chemical elemental concentration tendency in some extract relatively to others. The data obtained demonstrated that elemental chemicals are included in the structure of molecules encountered in the extracts. It was possible evaluate the nutrition contributions for the popular use forms. The results suggests a realization of epidemiological study to verify the real nutrition contribution and/or undesirable effects of Talinum patens.

Em cumprimento às normas que regulam a transferência e deposição final de rejeitos radioativos, o inventário de radionuclídeos de cada embalado contendo tais rejeitos deve ser estimado e declarado. Os limites autorizados são definidos em função das doses de radiação que indivíduos do público podem vir a receber anualmente a partir do repositório. Tais limites se referem principalmente às concentrações de atividade, dadas em Bq/g, dos radionuclídeos presentes nos embalados com rejeitos. A grande maioria dos radionuclídeos emissores de raios-gama pode ter a respectiva concentração de atividade determinada diretamente por medidas externas aos embalados. Entretanto, determinação análoga para os radionuclídeos emissores exclusivos de partículas alfa ou beta, bem como de alguns emissores de raios-gama e/ou raios-X cuja energia, intensidade absoluta de emissão e/ou atividade são muito baixas denominados genericamente Radionuclídeos de Difícil Medição (RDMs) requer procedimentos radioquímicos complexos para isolar a espécie química de interesse dos interferentes presentes nas matrizes de rejeitos. Ademais, nesse caso é necessário coletar amostras de cada embalado, acarretando elevadas doses de radiação para os operadores e altos custos logísticos, decorrentes do grande número de embalados com rejeitos radioativos que necessitam de caracterização em uma instalação nuclear. Uma metodologia alternativa para abordar esse problema consiste em obter correlações empíricas entre alguns radionuclídeos possíveis de serem medidos diretamente, como 60Co e 137Cs denominados Radionuclídeos Chave (RCs) e os RDMs. Essa metodologia, denominada Fator de Escala, foi aplicada no presente trabalho com a finalidade de determinar tais correlações, na forma de Fatores de Escala ou Funções de Correlação, para os principais rejeitos de baixa e média atividades do reator nuclear de pesquisa IEA-R1. / Regulations regarding transfer and final disposal of radioactive waste require that the inventory of radionuclides for each container enclosing such waste must be estimated and declared. The regulatory limits are established as a function of the annual radiation doses that members of the public could be exposed to from the radioactive waste repository, which mainly depend on the activity concentration of radionuclides, given in Bq/g, found in each waste container. Most of the radionuclides that emit gamma-rays can have their activity concentrations determined straightforwardly by measurements carried out externally to the containers. However, radionuclides that emit exclusively alpha or beta particles, as well as gamma-rays or X-rays with low energy and low absolute emission intensity, or whose activity is very low among the radioactive waste, are generically designated as Difficult to Measure Nuclides (DTMs). The activity concentrations of these DTMs are determined by means of complex radiochemical procedures that involve isolating the chemical species being studied from the interference in the waste matrix. Moreover, samples must be collected from each container in order to perform the analyses inherent to the radiochemical procedures, which exposes operators to high levels of radiation and is very costly because of the large number of radioactive waste containers that need to be characterized at a nuclear facility. An alternative methodology to approach this problem consists in obtaining empirical correlations between some radionuclides that can be measured directly such as 60Co and 137Cs, therefore designated as Key Nuclides (KNs) and the DTMs. This methodology, denominated Scaling Factor, was applied in the scope of the present work in order to obtain Scaling Factors or Correlation Functions for the most important radioactive wastes with low and intermediate-activity level from the IEA-R1 nuclear research reactor.