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Translation of new 18 F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18 F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18 F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [ 18 F]fluoride of human doses of [ 18 F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [ 18 F]5-fluorouracil precursor. Routine production of &gt;10 mCi doses of [ 18 F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [ 18 F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18 F-fluorination.

A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging

A Transmetalation Reaction Enables the Synthesis of [¹⁸F]5-Fluorouracil from [¹⁸F]Fluoride for Human PET Imaging