Made available in DSpace on 2014-10-09T12:38:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:05:01Z (GMT). No. of bitstreams: 1 05829.pdf: 3993449 bytes, checksum: f55d718241e0482c76629c4d48cbb722 (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

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Made available in DSpace on 2014-10-09T12:38:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:05:01Z (GMT). No. of bitstreams: 1 05829.pdf: 3993449 bytes, checksum: f55d718241e0482c76629c4d48cbb722 (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:26:13Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:09Z (GMT). No. of bitstreams: 0 / O aumento da demanda no Brasil pelo radiofármaco [18F]FDG para exames de tomografia por emissão de pósitron (PET-CT) e sua meia-vida de 109,7 minutos exigem uma atenção especial para a cadeia produtiva deste radiofármaco. Desde a irradiação da água enriquecida em 18O até a passagem do paciente pelo tomógrafo, numa seqüência de procedimentos que pode durar até cerca de seis horas, todas as etapas da cadeia produtiva devem ter a maior confiabilidade possível, pois qualquer falha em uma das etapas será sentida na extremidade da cadeia produtiva. A falta de indicação de posição da válvula do Sistema de Carga e Descarga do Porta-alvo de 18F- no Centro de Aceleradores Cíclotron levou a perda de produção de 18F-, contaminação da Sala de Irradiação e aumento da dose dos trabalhadores envolvidos na operação e manutenção dos sistemas de irradiação. Este trabalho testou o comportamento de três tipos de sensores de posição (microswitch, reedswitch e sensor de proximidade indutivo) no ambiente da Sala de Irradiação 1.2 do Centro de Aceleradores Cíclotron, que está sujeito a altas taxas de radiação gama e nêutrons devido à produção rotineira de 18F- e 123I, através deste teste foi possível encontrar o sensor de posição mais adequado para trabalhar no porta-alvo de 18F-, e através da reprogramação do controlador lógico programável, foi possível evitar este tipo de falha durante a produção de 18F- no Centro de Aceleradores Cíclotron, e aumentar a confiabilidade na cadeia produtiva do [18F]FDG. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

The main electrophilic source used in radiolabelling is [18F]F2, which is highly reactive, toxic and requires specialist equipment for safe handling. The Gouverneur group has initiated a research programme focused on the preparation of new stable and easy-to-handle N-18F reagents. In the development of [18F]radiolabelling reactions it would be extremely valuable to develop a library of selective N-18F reagents possessing reactivity tailored to the desired chemical transformation. The aim of this thesis is to further assess the scope of electrophilic N- 18F reagents in new transformations for the construction of C-18F bonds.

The expansion of [¹⁸F]-radiolabelling methodologies is vital for the advancement of Positron Emission Tomography (PET) as a medical imaging tool. Novel protocols will simplify access to current PET tracers and allow development of original tracers, potentially enhancing the imaging quality or permit imaging of a wider range of clinical problems. A general introduction is presented in <b>Chapter 1</b>, covering PET, application of fluorine-19 in the pharmaceutical industry, the production of fluorine-18 and the current state-of -art for [¹⁸F]-radiolabelling. The results chapters are divided in to two parts; <b>Part 1</b> (<b>Chapters 2 - 4</b>) concern the synthesis of [18F]fluoroarenes and <b>Part II</b> (<b>Chapters 5</b> and <b>6</b>) discuss diversity oriented radiofluorination techniques, targeting novel [¹⁸F]motifs. In <b>Part I</b>, Chapter 2 describes the use of hypervalent iodine reagents to meditate an umpolung approach for fluorination and radiofluorination of N-arylsulfonamides and anilides. <b>Chapter 3</b> again utilises hypervalent iodine reagents, but as spirocyclic iodonium(III) ylide precursors, being applied to semi-automated and automated microfluidic conditions. <b>Chapter 4</b> discusses the development of conditions for the production and isolation of radiopharmaceuticals employing Cu(II)-mediated radiofluorination of aryl boronic pinacol esters. In <b>Part II, Chapter 5</b> discusses the applicability of halogen exchange reactions to reach polyfluorinated motfis and <b>Chapter 6</b> focuses on the application of a single diazo precursor to access three polyfluorinated motifs with single-step reactions. Finally, <b>Chapter 7</b> provides experimental data for compounds discussed in this thesis.

No description available.

This work improved the radiosynthesis of a known M2 muscarinic receptor imaging agent, [18F]FP-TZTP, and subsequent syntheses and in vitro evaluation of several novel TZTP derivatives highlighted a lead compound which exhibited M4 potency and selectivity, the thioether fluoro-polyethyleneglycol, which was then adapted for radiolabelling (23% radiochemical yield (uncorrected), >99% radiochemical purity, reaction time of 37 minutes). The present study also seeked to utilize aziridines as intermediates in [18F]-radiolabelling chemistry for the facile radiosynthesis of [18F]-labelled beta-blockers. Novel [18F]-labelled amines were synthesized via ring-opening and deprotection to yield the [18F]-1-fluoro-2-propanamine moiety (85%) favourably over the regioisomer [18F]-2-fluoro-1-propanamine (15%). Subsequent attempts to use these amine synthons in the synthesis of the beta-blocker [18F]Exaprolol resulted in poor radiochemical yields (1-3%). The chemistry of aziridine ring-opening with 19F-fluoride sources was thoroughly explored in order to understand the fundamentals of this chemistry, and the 1-fluoro-2-propanamine moiety was characterized by X-ray crystallography and NMR spectroscopy.

This work improved the radiosynthesis of a known M2 muscarinic receptor imaging agent, [18F]FP-TZTP, and subsequent syntheses and in vitro evaluation of several novel TZTP derivatives highlighted a lead compound which exhibited M4 potency and selectivity, the thioether fluoro-polyethyleneglycol, which was then adapted for radiolabelling (23% radiochemical yield (uncorrected), >99% radiochemical purity, reaction time of 37 minutes). The present study also seeked to utilize aziridines as intermediates in [18F]-radiolabelling chemistry for the facile radiosynthesis of [18F]-labelled beta-blockers. Novel [18F]-labelled amines were synthesized via ring-opening and deprotection to yield the [18F]-1-fluoro-2-propanamine moiety (85%) favourably over the regioisomer [18F]-2-fluoro-1-propanamine (15%). Subsequent attempts to use these amine synthons in the synthesis of the beta-blocker [18F]Exaprolol resulted in poor radiochemical yields (1-3%). The chemistry of aziridine ring-opening with 19F-fluoride sources was thoroughly explored in order to understand the fundamentals of this chemistry, and the 1-fluoro-2-propanamine moiety was characterized by X-ray crystallography and NMR spectroscopy.

Made available in DSpace on 2014-10-09T12:35:12Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:12Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP / FAPESP:11/03138-8