CO₂ fixation: a renaissance in PET radiochemistry

Carbon-11 labelled carbon dioxide is the cyclotron-generated feedstock reagent for most positron emission tomography (PET) tracers using this radionuclide. Most carbon-11 labels, however, are installed using derivative reagents generated from [¹¹C]CO₂. In recent years, [¹¹C]CO₂ has seen a revival in applications for the direct incorporation of carbon-11 into functional groups such as ureas, carbamates, oxazolidinones, carboxylic acids, esters, and amides. This review summarizes classical [¹¹C]CO₂ fixation strategies using organometallic reagents and then focuses on newly developed methods that employ strong organic bases to reversibly capture [¹¹C]CO₂ into solution, thereby enabling highly functionalized labelled compounds to be prepared. Labelled compounds and radiopharmaceuticals that have been translated to the clinic are highlighted.