Positron emission tomography (PET) employs short half-life positron emitting isotopes, typically <sup>18</sup>F, for in vivo measurement of physiological processes. Easy access to structurally diverse radiolabelled probes would accelerate the rapid progress of PET imaging but, to date, radiochemistry is still limited by cost and efficiency. Nucleophilic fluorination with <sup>18</sup>F-fluoride is the preferred “non-carrier-added” methodology in the synthesis of <sup>18</sup>F-labelled pharmaceuticals because it leads to radiotracers with a high specific activity, a key feature allowing for investigations to be performed in sub-toxic doses. Chapter 1 serves as an introduction on radiochemistry, especially focussing on current radiosynthetic methods for the synthesis of <sup>18</sup>F-labelled aromatics. Aromatic compounds without electron-withdrawing groups are notoriously difficult to label with <sup>18</sup>F-fluoride. In this thesis, we present two novel methodologies to deliver <sup>18</sup>F-labelled aromatic compounds from nucleophilic 18F-fluoride. Chapter 2 details the experimental efforts towards “Convergent Radiosynthesis” (Scheme 1). We proposed a convergent synthetic tactic that allows for simultaneous reaction between three or more substrates, including an <sup>18</sup>F-labelled building block. This chemistry has been validated by the radiosynthesis of various structural scaffolds which are not responsive to direct nucleophilic fluorination. Chapter 3 presents our research into “Oxidative Nucleophilic <sup>18</sup>F-Fluorination” (Scheme 2). We proposed that electron-rich aromatics, such as phenols, which are not responsive to nucleophilic fluorination may undergo umpolung reactivity under oxidative conditions. This “umpolung strategy” allows for the direct transformation from <sup>18</sup>F-fluoride to 4-[<sup>18</sup>F]fluorophenol. Potentially, this established oxidative fluorination strategy could be adapted to the radiosynthesis of radiotracers containing a 4-fluorophenol sub-motif, such as 6-fluoro-meta-tyrosine. An appropriate precursor has been validated for the prospective radiosynthesis of 6-[18F]fluoro-meta-tyrosine.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558446 |
| Date | January 2011 |
| Creators | Li, Lei |
| Contributors | Gouverneur, Veronique |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:000fd696-e283-4233-8646-f6f17833c826 |
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