Recent Advances in C-Labeling With [C]CO for PET Imaging.

Carbon-11 (C)-labeled radiotracers are invaluable tools in positron emission tomography (PET), enabling real-time visualization of biochemical processes with high sensitivity and specificity. Among the various C synthons, cyclotron-produced [C]CO is a fundamental precursor, though its direct incorporation into complex molecules has traditionally been limited by its low reactivity, gaseous form, and short half-life. Recent advances in [C]CO fixation chemistry through both nonphotocatalytic and photocatalytic methods have significantly expanded its utility in the synthesis of structurally diverse compounds, including carboxylic acids, carbonates, carbamates, amides, and ureas. This review summarizes key developments in [C]CO radiolabeling strategies, with critical evaluation of substrate scope, radiochemical yield, molar activity, and clinical translation potential. These advances collectively expand the synthetic versatility of [C]CO and pave the way for the development of structurally diverse and clinically translatable PET imaging agents.