11C=O bonds made easily for positron emission tomography radiopharmaceuticals

The positron-emitting radionuclide carbon-11 (C-11, t(1/2) = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [C-11] methyl iodide or [C-11] methyl triflate (generated from [C-11] carbon dioxide or [C-11]methane). Consequently, small molecules that lack an easily substituted C-11-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [C-11] Carbon dioxide itself, [C-11] carbon monoxide, [C-11] cyanide, and [C-11] phosgene represent alternative reactants to enable C-11-carbonylation. Methodologies developed for preparation of C-11-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. C-11-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry.