Ritter, TobiasHoover, Andrew2015-12-042015-112015-07-202015Hoover, Andrew. 2015. A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil From [18F]Fluoride for Human PET Imaging. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.http://nrs.harvard.edu/urn-3:HUL.InstRepos:238454085-Fluorouracil is a broad-spectrum chemotherapeutic for cancer treatment. [18F]5-Fluorouracil, which contains the radioactive isotope fluorine-18, is a tracer for positron emission tomography (PET) imaging and has been applied for determining the location over time of 5-fluorouracil in the bodies of human cancer patients. Potential applications of [18F]5-fluorouracil are for personalized chemotherapy and the development of new cancer treatments. All reported preparations of [18F]5-fluorouracil for human PET imaging have used [18F]F2 gas, which is challenging to produce and handle, and is less desired as a starting material in comparison to [18F]fluoride. This dissertation describes the development and translation of new chemical reactions to produce human doses of [18F]5-fluorouracil from [18F]fluoride. The first preparation of nickel(II) σ-aryl complexes by transmetalation from arylboronic acids was developed. This transmetalation reaction was applied to produce a nickel(II) σ-aryl complex that undergoes oxidative fluorination with [18F]fluoride for the synthesis of [18F]5-fluorouracil. This oxidative fluorination reaction was translated for production of human doses of [18F]5-fluorouracil. Although numerous transition metal-mediated fluorination reactions have been developed, none have previously been translated to enable human PET imaging.application/pdfenChemistry, OrganicThesis or Dissertation2016-11-01