The sydnone-dibenzocyclooctyne and norbornene-tetrazine cycloadditions are both bioorthogonal and mutually orthogonal, used for simultaneous labeling of two targets.
Translation
of new 18F-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 18F-labeled tracer production must be robust and simple
to execute. The application of transition metal mediators has enabled
impactful 18F-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 [18F]fluoride
of human doses of [18F]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 [18F]5-fluorouracil
precursor. Routine production of >10 mCi doses of [18F]5-fluorouracil
was accomplished with a new instrument for azeotrope-free [18F]fluoride concentration in a process that leverages the tolerance
of water in nickel-mediated 18F-fluorination.
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