Este trabalho tem como objetivo realizar a caracterização do campo de nêutrons e radiação gama na posição de irradiação de amostras em uma instalação para pesquisas em Terapia por Captura de Nêutrons em Boro (BNCT) no IPEN, junto ao reator IEA-R1. A técnica de BNCT vem sendo estudada como uma opção seletiva e segura de tratamento para tumores cancerígenos resistentes ou considerados não tratáveis pelas técnicas convencionais, por exemplo, o Glioblastoma Multiforme - tumor cancerígeno no cérebro. Foram realizadas medições de fluxos de nêutrons térmicos, epitérmicos e rápidos bem como das doses devido a nêutrons, e radiação gama na posição de amostra, utilizando-se detectores de ativação tipo folha e dosímetros termoluminescente. Para determinação da intensidade e do espectro de energia de nêutrons, foi utilizado um conjunto de folhas de ativação de energias limiares distintas, irradiadas na instalação e analisadas com um detetor semicondutor de Germânio hiper puro acoplado a um sistema eletrônico adequado para espectrometria gama e os resultados processados com o código SAND-BP. As doses devidas a radiação gama e nêutrons foram determinadas utilizando dosímetros termoluminescentes: TLD-400 (sensível a gama); TLD-600 (sensível a nêutrons) e TLD-700 (sensível a gama). Os TLDs foram selecionados e usados para a obtenção das curvas de calibração - resposta do dosímetro versus dose - de cada uma dos três tipos de TLD, as quais foram utilizadas para calcular as doses devidas a nêutrons e gama na posição de amostra. O campo de radiação na posição de irradiação de amostra foi caracterizado fluxo para nêutrons térmicos de 1.39.108 ± 0,12.108 n/cm2s a dose devido a nêutrons térmicos é três vezes maior que as devido a radiação gama, essas medidas comprovam a reprodutibilidade e consistência dos resultados experimentais obtidos. Considerando os resultados obtidos, verificou-se que o campo de nêutrons e radiação gama atende para pesquisa em BNCT. NEUTRON / This work aims to characterize the mixed neutron and gamma field, in the sample irradiation position, in a research installation for Boron Neutron Capture Therapy (BNCT), in the IPEN IEA-R1 reactor. The BNCT technique has been studied as a safe and selective option in the treatment of resistant cancerigenous tumors or considered non-curable by the conventional techniques, for example, the Glioblastoma Multiform a brain cancerigenous tumor. Neutron flux measurements were carried out: thermal, ressonance and fast, as well as neutron and gamma rays doses, in the sample position, using activation foils detectors and thermoluminescent dosimeters. For the determination of the neutron spectrum and intensity, a set of different threshold activation foils and gold foils covered and uncovered with cadmium irradiated in the installation was used, analyzed by a high Pure Germanium semiconductor detector, coupled to an electronic system suitable for gamma spectrometry. The results were processed with the SAND-BP code. The doses due to gamma and neutron rays were determined using thermoluminescent dosimeters TLD 400 and TLD 700 sensitive to gamma and TLD 600, sensitive to neutrons. The TLDs were selected and used for obtaining the calibration curves dosimeter answer versus dose from each of the TLD three types, which were necessary to calculate the doses due to neutron and gamma, in the sample position. The radiation field, in the sample irradiation position, was characterized flux for thermal neutrons of 1.39.108 ± 0,12.108 n/cm2s the doses due to thermal neutrons are three times higher than those due to gamma radiation and confirm the reproducibility and consistency of the experimental findings obtained. Considering these results, the neutron field and gamma radiation showed to be appropriated for research in BNCT

A Terapia por Captura de Nêutrons, NCT (Neutron Capture Therapy) é uma técnica radioterápica em que a energia útil do tratamento vem da energia liberada em uma reação nuclear e não do feixe primário, como comumente utilizado em outros procedimentos radioterápicos. O Boro, por constituir-se em um elemento de baixa toxicidade e por apresentar um isótopo (10B) com alta seção de choque para a reação 10B(n,α)7Li tem sido o elemento mais utilizado nas pesquisas que visam o aprimoramento e a promoção desta técnica, derivando daí o termo BNCT (Boron Neutron Capture Therapy). Para fins de pesquisa em BNCT foi construída ao longo de um dos extratores de feixes (BH - Beam Hole) do reator IEA-R1 uma instalação, onde filtros e moderadores são posicionados entre o núcleo do reator e a posição de irradiação com o objetivo de modular o feixe de irradiação, otimizando a componente útil do feixe, os nêutrons térmicos, e reduzindo os contaminantes, raios gama e nêutrons em outras faixas energéticas. Tem-se realizado estudos visando a implementação de melhorias na caracterização e otimização do feixe obtido nesse arranjo instalado no BH-3. Atualmente a monitoração dos nêutrons é feita através de folhas de ativação, e a componente gama pelo TLD-400. Uma nova metodologia de monitoração tem sido estudada pelo grupo. A referida técnica consiste em usar TLDs de tipos diferentes, ou seja, que possuam sensibilidades distintas aos nêutrons térmicos, em virtude de diferenças na concentração dos isótopos de Lítio. No estudo dessa nova metodologia têm sido usados os TLD-600 e TLD-700. Este trabalho propõe uma metodologia usando o par TLD-100 e TLD-700. Inicialmente foi verificada a reprodutibilidade das respostas dos TLDs 700, 400 e 100 frente a campos gama puro e campos mistos, gama e nêutron. Campos estes obtidos em arranjos usando fontes de 60Co e 241AmBe. A partir de simulações usando o VI MCNP5 foi projetado e construído um Irradiador de campos mistos, que permitiu expor os dosímetros em campos mistos com diferentes espectros energéticos. As condições criadas no irradiador permitiram verificar, como a resposta do TLD é modificada pelas mudanças no espectro energético de um campo misto gama e nêutrons de baixo fluxo. O irradiador de campo misto permitiu condições para estabelecer uma relação entre o formato da curva termoluminescente e a composição do campo misto. A relação estabelecida relaciona o fluxo relativo e a razão entre a resposta das duas regiões de interesse dos TLDs 700 e 100. A partir de campos mistos com condições controladas, esse trabalho permitiu verificar a viabilidade do uso do par de TLD-100 e TLD-700 para monitoração de nêutrons térmicos na instalação de BNCT. / Neutron Capture Therapy (NCT), is a radiotherapy technique in which the useful treatment energy comes from the energy released in a nuclear reaction and not from the primary beam, as commonly used in other radiotherapc procedures. Boron, an element of low toxicity presents an isotope (10B) with high cross-section for the (n, α) reaction and therefore has been the element mostly used in research aimed at the improvement and promotion of this technique, deriving hence the term BNCT (Boron Neutron Capture Therapy). For BNCT research purposes, a facility was built along one of radiation extractors of the IEA-R1 reactor. In this facility filters and moderators are positioned between the reactor core and the irradiation position aiming to modulate the irradiation beam by optimizing the useful component of the beam, thermal neutrons, and reducing its contaminants, gamma rays and neutrons in higher energy bands. We have conducted studies aimed at implementing improvements in the characterization of and optimization of the beam. Currently, neutron flux monitorion is done through activation foils, and the gamma component by TLD-400. A new methodology has been studied by the group. The technique consists in using different types of TLD, having different sensitivities to thermal neutrons due to differences in the concentration of lithium isotopes. In the study of this new methodology TLD 600 and TLD-700 have been used. This work presents a series of studies in order to apply a methodology using the TLD-100 and TLD-700 pair. TLDs 700, 400 and 100 responses pure gamma and mixed irradiation fields, obtained in arrangements using a 60Co and AmBe sources, were evaluaterd. MCNP simulations were run in order to both discriminating the radiation components and designing one mixed fields irradiator, which allowed exposing dosimeters in mixed fields with different energy spectra. The conditions created in the irradiator allowed to verify, as the TLD response is modified by changes in the energy spectrum of a mixed gamma neutron fields. VIII This irradiator provided irradiation conditions so to establish a relationship between the shape of the LiF glow curves and the composition of the mixed field. This work has shown the feasibility of using the TLD-100 and TLD-700 pair for gamma and thermal neutrons monitoration in the BNCT facility.

A instalação do IPEN para pesquisas em BNCT (Terapia por Captura de Nêutrons em Boro) utiliza o canal de irradiação número 3 do reator IEA-R1, no qual tem-se um campo misto de radiação nêutrons e gama. As pesquisas em andamento necessitam que o campo de radiação, na posição de irradiação de amostra, tenha na composição os nêutrons térmicos maximizados e os componentes de nêutrons epitérmicos, rápidos e radiação gama minimizados. Este trabalho foi desenvolvido com o objetivo de avaliar se o campo de radiação atual na instalação é adequado aos trabalhos em BNCT. Para cumprir com este objetivo, uma metodologia para dosimetria de nêutrons térmicos e radiação gama em campos mistos de altas doses, que não era disponível no IPEN, foi implantada no Centro de Engenharia Nuclear do IPEN, utilizando dosímetros termoluminescentes TLDs 400, 600 e 700. Para as medidas de fluxo de nêutrons térmicos e epitérmicos foram utilizados detetores de ativação de ouro aplicando a técnica de razão de cádmio. Um simulador antropomórfico cilíndrico composto de discos de acrílico foi desenvolvido e testado na instalação e para obter valores teóricos do fluxo de nêutrons e a dose ao longo do simulador antropomórfico foi utilizado o código computacional DOT 3.5. Na posição correspondente a aproximadamente metade do comprimento do cilindro do simulador antropomórfico, foram obtidos os seguintes valores: fluxo de nêutrons térmicos (2,52 ± 0,06).108n/cm2s, epitérmicos (6,17 ± 0,26).107n/cm2s, dose absorvida devido a nêutrons térmicos de (4,2 ± 1,8)Gy e devido a radiação gama (10,1 ± 1,3)Gy. Os valores obtidos mostram que os fluxos de nêutrons térmicos e epitérmicos são adequados para os estudos em BNCT, porém, a dose devido a radiação gama está elevada, indicando que a instalação deve ser aprimorada. / IPEN facility for researches in BNCT (Boron Neutron Capture Therapy) uses IEA-R1 reactor\'s irradiation channel number 3, where there is a mixed radiation field neutrons and gamma. The researches in progress require the radiation fields, in the position of the irradiation of sample, to have in its composition maximized thermal neutrons component and minimized, fast and epithermal neutron flux and gamma radiation. This work was developed with the objective of evaluating whether the present radiation field in the facility is suitable for BNCT researches. In order to achieve this objective, a methodology for the dosimetry of thermal neutrons and gamma radiation in mixed fields of high doses, which was not available in IPEN, was implemented in the Center of Nuclear Engineering of IPEN, by using thermoluminescent dosimeters TLDs 400, 600 and 700. For the measurements of thermal and epithermal neutron flux, activation detectors of gold were used applying the cadmium ratio technique. A cylindrical phantom composed by acrylic discs was developed and tested in the facility and the DOT 3.5. computational code was used in order to obtain theoretical values of neutron flux and the dose along phantom. In the position corresponding to about half the length of the cylinder of the phantom, the following values were obtained: thermal neutron flux (2,52 ± 0,06).108n/cm2s, epithermal neutron flux (6,17 ± 0,26).107.106n/cm2s, absorbed dose due to thermal neutrons (4,2 ± 1,8)Gy and (10,1 ± 1,3)Gy due to gamma radiation. The obtained values show that the fluxes of thermal and epithermal neutrons flux are appropriate for studies in BNCT, however, the dose due to gamma radiation is high, indicating that the facility should be improved.

A instalação do IPEN para pesquisas em BNCT (Terapia por Captura de Nêutrons em Boro) utiliza o canal de irradiação número 3 do reator IEA-R1, no qual tem-se um campo misto de radiação nêutrons e gama. As pesquisas em andamento necessitam que o campo de radiação, na posição de irradiação de amostra, tenha na composição os nêutrons térmicos maximizados e os componentes de nêutrons epitérmicos, rápidos e radiação gama minimizados. Este trabalho foi desenvolvido com o objetivo de avaliar se o campo de radiação atual na instalação é adequado aos trabalhos em BNCT. Para cumprir com este objetivo, uma metodologia para dosimetria de nêutrons térmicos e radiação gama em campos mistos de altas doses, que não era disponível no IPEN, foi implantada no Centro de Engenharia Nuclear do IPEN, utilizando dosímetros termoluminescentes TLDs 400, 600 e 700. Para as medidas de fluxo de nêutrons térmicos e epitérmicos foram utilizados detetores de ativação de ouro aplicando a técnica de razão de cádmio. Um simulador antropomórfico cilíndrico composto de discos de acrílico foi desenvolvido e testado na instalação e para obter valores teóricos do fluxo de nêutrons e a dose ao longo do simulador antropomórfico foi utilizado o código computacional DOT 3.5. Na posição correspondente a aproximadamente metade do comprimento do cilindro do simulador antropomórfico, foram obtidos os seguintes valores: fluxo de nêutrons térmicos (2,52 ± 0,06).108n/cm2s, epitérmicos (6,17 ± 0,26).107n/cm2s, dose absorvida devido a nêutrons térmicos de (4,2 ± 1,8)Gy e devido a radiação gama (10,1 ± 1,3)Gy. Os valores obtidos mostram que os fluxos de nêutrons térmicos e epitérmicos são adequados para os estudos em BNCT, porém, a dose devido a radiação gama está elevada, indicando que a instalação deve ser aprimorada. / IPEN facility for researches in BNCT (Boron Neutron Capture Therapy) uses IEA-R1 reactor\'s irradiation channel number 3, where there is a mixed radiation field neutrons and gamma. The researches in progress require the radiation fields, in the position of the irradiation of sample, to have in its composition maximized thermal neutrons component and minimized, fast and epithermal neutron flux and gamma radiation. This work was developed with the objective of evaluating whether the present radiation field in the facility is suitable for BNCT researches. In order to achieve this objective, a methodology for the dosimetry of thermal neutrons and gamma radiation in mixed fields of high doses, which was not available in IPEN, was implemented in the Center of Nuclear Engineering of IPEN, by using thermoluminescent dosimeters TLDs 400, 600 and 700. For the measurements of thermal and epithermal neutron flux, activation detectors of gold were used applying the cadmium ratio technique. A cylindrical phantom composed by acrylic discs was developed and tested in the facility and the DOT 3.5. computational code was used in order to obtain theoretical values of neutron flux and the dose along phantom. In the position corresponding to about half the length of the cylinder of the phantom, the following values were obtained: thermal neutron flux (2,52 ± 0,06).108n/cm2s, epithermal neutron flux (6,17 ± 0,26).107.106n/cm2s, absorbed dose due to thermal neutrons (4,2 ± 1,8)Gy and (10,1 ± 1,3)Gy due to gamma radiation. The obtained values show that the fluxes of thermal and epithermal neutrons flux are appropriate for studies in BNCT, however, the dose due to gamma radiation is high, indicating that the facility should be improved.

Yes / Boron neutron capture therapy (BNCT) has a long history of unfulfilled promises for the treatment of aggressive cancers. In the last two decades, chemists, physicists, and clinical scientists have been coordinating their efforts to overcome practical and scientific challenges needed to unlock its full therapeutic potential. From a chemistry point of view, the two current small-molecule drugs used in the clinic were developed in the 1950s, however, they both lack some of the essential requirements for making BNCT a successful therapeutic modality. Novel strategies are currently used to design new drugs, more selective towards cancer cells and tumours, as well as able to deliver high boron contents to the target. In this context, macromolecules, including polymers, are promising tools to make BNCT an effective, accepted, and front-line therapy against cancer. In this review, we will provide a brief overview of BNCT, and its potential and challenges, and we will discuss the most promising strategies that have been developed so far.

Es besteht ein großer Bedarf an einer Therapie für Krebserkrankungen mit diffusen, nicht operablen Metastasen an vitalen Organen. Bei Metastasenbildung werden die Patienten im Allgemeinen nicht für eine Transplantation mit Spenderorganen vorgesehen. Das bedeutet, bei Nichtansprechen einer Chemotherapie gibt es derzeit keine Therapiealternative für diese Patienten. Wenn eine Transplantation der betroffenen Organe möglich ist, besteht eine Chance für die Anwendung eines neuen therapeutischen Konzeptes. Dieses Konzept basiert auf der Bestrahlung des isolierten Organs (Autotransplantation) mittels der Bor-Neutronen-Einfang-Therapie (BNCT). Das betreffende Organ des Patienten wird dabei zeitweise explantiert und in diesem Zeitraum einer Bestrahlungstherapie unterzogen. Diese Therapieform erfordert kein Spenderorgan und es kann dementsprechend auch zu keinen Abstoßungsreaktionen des Immunsystems durch körperfremdes Gewebe kommen. Erstmalig wurde dieses Verfahren im Dezember 2001 an der Universität Pavia an einem Patienten erfolgreich durchgeführt und damit die prinzipielle Machbarkeit belegt. Bis heute wurde in Pavia noch ein weiterer Patient mit diesem Verfahren behandelt. Nach diesen ersten Heilungsversuchen ist es jetzt erforderlich den therapeutischen Nutzen der Methode reproduzierbar nachzuweisen und diese dann für die Routineanwendung verfügbar zu machen. Das ist eine wesentliche Voraussetzung für die erfolgreiche Einführung dieser Therapieform. Im Rahmen dieser Arbeit soll eine für diese Therapieform optimierte Bestrahlungseinrichtung entwickelt werden. Als Referenzorgan wird die Leber betrachtet, aufgrund ihrer hohen Wahrscheinlichkeit für eine Metastasenbildung, des Mangels an Spenderorganen und fehlender Therapiealternativen. Als geeignete Referenzneutronenquelle bietet sich der TRIGA-Reaktor an. Für diesen Reaktortyp wird die Bestrahlungseinrichtung mit technischen Details und Abmessungen konzipiert.

Es besteht ein großer Bedarf an einer Therapie für Krebserkrankungen mit diffusen, nicht operablen Metastasen an vitalen Organen. Bei Metastasenbildung werden die Patienten im Allgemeinen nicht für eine Transplantation mit Spenderorganen vorgesehen. Das bedeutet, bei Nichtansprechen einer Chemotherapie gibt es derzeit keine Therapiealternative für diese Patienten. Wenn eine Transplantation der betroffenen Organe möglich ist, besteht eine Chance für die Anwendung eines neuen therapeutischen Konzeptes. Dieses Konzept basiert auf der Bestrahlung des isolierten Organs (Autotransplantation) mittels der Bor-Neutronen-Einfang-Therapie (BNCT). Das betreffende Organ des Patienten wird dabei zeitweise explantiert und in diesem Zeitraum einer Bestrahlungstherapie unterzogen. Diese Therapieform erfordert kein Spenderorgan und es kann dementsprechend auch zu keinen Abstoßungsreaktionen des Immunsystems durch körperfremdes Gewebe kommen. Erstmalig wurde dieses Verfahren im Dezember 2001 an der Universität Pavia an einem Patienten erfolgreich durchgeführt und damit die prinzipielle Machbarkeit belegt. Bis heute wurde in Pavia noch ein weiterer Patient mit diesem Verfahren behandelt. Nach diesen ersten Heilungsversuchen ist es jetzt erforderlich den therapeutischen Nutzen der Methode reproduzierbar nachzuweisen und diese dann für die Routineanwendung verfügbar zu machen. Das ist eine wesentliche Voraussetzung für die erfolgreiche Einführung dieser Therapieform. Im Rahmen dieser Arbeit soll eine für diese Therapieform optimierte Bestrahlungseinrichtung entwickelt werden. Als Referenzorgan wird die Leber betrachtet, aufgrund ihrer hohen Wahrscheinlichkeit für eine Metastasenbildung, des Mangels an Spenderorganen und fehlender Therapiealternativen. Als geeignete Referenzneutronenquelle bietet sich der TRIGA-Reaktor an. Für diesen Reaktortyp wird die Bestrahlungseinrichtung mit technischen Details und Abmessungen konzipiert.:1. Einleitung 2. Grundlagen 2.1 Krebserkrankungen der Leber 2.2 Makroskopischer und mikroskopischer Aufbau der Leber 2.3 Beschreibung der Therapieform BNCT 2.4 Biologische Wirkung der Bestrahlung 2.5 Dosiswirkungsbeziehungen 2.6 Kinetik des B-10-Pharmakons 2.7 TRIGA-Reaktor als Referenzneutronenquelle 2.8 Vorgehen beim Aufbau einer Strahlentherapie 2.9 Vorgehen für die Auslegung und Optimierung der spezifischen Bestrahlungseinrichtung am TRIGA-Reaktor in Mainz 2.10 Ausblick 3. Dosimetrie 3.1 Strahlungsfeldgrößen und Dosisbegriff 3.2 Wechselwirkungen der Strahlung mit Materie 3.2.1. Wechselwirkung von Neutronen mit Materie 3.2.2. Wechselwirkung von Photonen mit Materie 3.2.3. Wechselwirkung von Protonen, alpha-Teilchen und Elektronen mit Materie 3.3 Berechnung des Strahlentransportes und der Strahlungsfeldgrößen 3.4 Berechnung der Dosis aus den Strahlungsfeldgrößen 3.5 Berechnung der gewichteten Gesamtdosis und der Dosisanteile der BNCT 4. Anforderungen an die Bestrahlungseinrichtung 4.1 Anforderungen der Therapieform 4.2 Anforderungen aus medizinischer Sicht 4.3 Anforderungen des Medizinproduktegesetzes (MPG) und der zugehörigen Richtlinie 93/42/EWG 4.4 Anforderungen der Referenz-Neutronenquelle 4.4.1 Atomgesetz (AtG) und Verordnungen 4.4.2 Strahlenschutzverordnung (StrlSchV) 5. Programme 5.1 MCNP 5.2 ATTILA 5.3 SCALE 6. Basisdaten für die Berechnungen 6.1 Leber 6.2 TRIGA Mark II Reaktor in Mainz 6.2.1 Aufbau 6.2.2 Abmessungen 6.2.3 Materialien 6.2.4 Leistungshistorie 6.2.5 Energiespektrum und Stärke der Quelle 6.2.6 Vereinfachungen und Randbedingungen 6.3 Wirkungsquerschnitte 7. Rechenmodelle 7.1 Modell zur Bestimmung optimaler Parameter für die Therapieform 7.2 Modelle des TRIGA Mark II Reaktors in Mainz 7.2.1 Modell zur Bestimmung der Quellverteilung 7.2.2 Modell zur Strahlcharakterisierung 7.2.3 Modell für die Bestimmung der Dosisanteile für das autotransplantierte Organ 8. Ergebnisse der Berechnungen 8.1 Darstellung der Ergebnisse 8.2 Optimale Parameter für die geplante Therapieform 8.2.1 Energieverteilung der Quelle 8.2.2 Ausdehnung, Intensitäts- und Winkelverteilung der Quelle 8.2.3 Positionierung des Organs im Strahlenfeld 8.2.4 Bor-Konzentration und Bor-Konzentrationsverhältnis 8.2.5 Zusammenfassung 8.3 Auslegung und Optimierung der Bestrahlungseinrichtung am TRIGA-Mark II Reaktor in Mainz 8.3.1 Charakteristik der Quelle 8.3.2 Festlegung der Position der Bestrahlungseinrichtung 8.3.3 Vergleich der Berechnungen mit Messungen 8.3.4 Optimierung der konstruktiven Ausführung 8.3.4.1 Kollimator 8.3.4.2 Absorber 8.3.4.3 Konverter 8.3.4.4 Filter 8.3.4.5 Abstand der Bestrahlungsposition von der Reaktorkernmitte 8.3.4.6 Zusammenfassung der optimierten konstruktiven Ausführung der Bestrahlungseinrichtung 8.3.5 Dosierungsfehler 8.3.5.1 Diskretisierungsfehler 8.3.5.2 Einfluss der Reaktorfahrweise 8.3.5.3 Einfluss der Aktivierung der Strukturmaterialien 8.4 Wärmebilanz 9. Optimierte Bestrahlungseinrichtung und Maßnahmen für den Umbau 10. Ablaufplan für die Therapie 11. Zielerreichung 12. Zusammenfassung 13. Literaturverzeichnis ANHANG

De nouveaux précurseurs borates-triéthoxysilanes comprenant le closo-decahydrodecaborate ont été préparés et immobilisés dans la silice. L'introduction des groupements trialkoxysilyles sur les clusters (NH4)2B10H10, a été réalisée par condensations électrophiles faisant appel à des réactifs nucléophiles dans des conditions douces, tout en épargnant l'utilisation d'électrophiles ou de catalyseurs coûteux. Les borates-trialkoxysilanes obtenus ont été caractérisés par RMN 1H, 13C, 11B, 29Si, 31P, IRTF, analyse élémentaire et spectroscopie de masse. Comme preuve de concept, ces précurseurs ont été incorporés de manière covalente dans les pores d'une silice mésoporeuse, SBA-15. Tous les matériaux hybrides mésoporeux et modifiés avec du borate-triéthoxysilane ont été caractérisés par RMN solide 11B et 29Si, DRX, MET, les analyses élémentaires et étude de l'adsorption d'azote (méthode BET). Les précurseurs silylés-borate ont été combinés avec des nanoparticules de silice pour une utilisation éventuelle dans BNCT, où des NPs d'environ 100 nm ont été synthétisées comprenant deux types de centres luminescents différents. FITC silylé (isothiocyanate de fluorescéine) et complexe Eu (III) silylé ont été respectivement immobilisés dans des nanoparticules de silice par le procédé sol-gel. Les deux types de nanoparticules luminescentes ont été fonctionnalisés par les groupes silylés-borates et caractérisés par RMN du solide 11B, 31P et 29Si, DLS, MET, analyses élémentaires, d'adsorption d'azote et spectrophotométrie. / New borate-triethoxysilane precursors comprising the closo-decahydrodecaborate cluster were prepared and immobolized into hybrid silica materials. The synthesis of silylated clusters starting from (NH4)2B10H10 and silane precursors R-Si(OEt)3 through Electrophilic Induced Nucleophilic Reactions was performed under mild conditions, the silylated clusters were analyzed by 1H, 13C, 11B, 29Si, 31P NMR, IR, elemental analyses and mass spectroscopy ES-ESI. As a proof of concept, the borate-triethoxysilane precursors were covalently incorporated into the pores of mesoporous silica, SBA-15 type. All mesoporous materials modified with borate-triethoxysilane were characterized by 11B and 29Si solid state NMR, XRD, TEM, elemental analyses and Nitrogen sorption studies. The silylated-borate precursors were combined with dye-doped silica nanoparticles for possible future use in BNCT technique, where ~100 nm nanoparticles were synthesized comprising two different types of luminescent centers. Silylated FITC (fluorescein isothiocyanate) and silylated Eu(III) complexes were embedded into silica nanoparticles through sol-gel process. Both types of luminescent nanoparticles were functionalized with the silylated-borate clusters and characterized by 11B, 31P and 29Si solid state NMR, DLS, TEM, elemental analyses, Nitrogen sorption studies and spectrophotometer.

This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising. The thesis can be divided into three parts: i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield. ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam. iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented. The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22441号 / 工博第4702号 / 新制||工||1734(附属図書館) / 京都大学大学院工学研究科原子核工学専攻 / (主査)教授 神野 郁夫, 教授 斉藤 学, 准教授 櫻井 良憲 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM