A Solid‐Phase Route to 18F‐Labeled Tracers, Exemplified by the Synthesis of [18F]2‐Fluoro‐2‐deoxy‐D‐glucose

Due to the short half-life of [18F] (half-life = 110min), the synthesis and purification ofradiotracers incorporating this positron-emitting radionuclide needs to be carried out as rapidly aspossible for applications in imaging using positron emission tomography (PET). Here we describe a conceptually new strategy for the synthesis of [18F]-containing molecules, which releases theradiotracer from a solid-supported precursor using limiting [18F]-fluoride. A major advantage overexisting solution methods lies in the fact that incorporation of the radionuclide occurs by means of nucleophilic displacement of a sulfonate ester linkage to the solid-phase, which occurs withconcomitant release of the radiotracer into solution. The vast excess of precursor that istraditionally employed remains attached to the solid-phase and is removed by simple filtration. The potential of the methodology is illustrated by the synthesis of the most important and widelyused [18F]-radiotracer 2-[18F]-fluoro-2-deoxyglucose (FDG) with good radiochemical yield (73%,decay corrected) and superior chemical purity.