[¹¹C]phosgene: Synthesis and application for development of PET radiotracers

Carbon-11-labeled phosgene ([¹¹C]phosgene, [¹¹C]COCl₂) is a useful labeling agent that connects two heteroatoms by inserting [¹¹C]carbonyl (¹¹C=O) function in carbamates, ureas, and carbonates, which are components of biologically important heterocyclic compounds and functional groups in drugs as a linker of fragments with in vivo stability. Development of ¹¹C-labeled PET tracers has been performed using [¹¹C]phosgene as a labeling agent. However, [¹¹C]phosgene has not been frequently used for ¹¹C-labeling because preparation of [¹¹C]phosgene required dedicated synthesis apparatus (not commercially available) and had problems in reproducibility and reliability. In our laboratory, an improved method for synthesizing [¹¹C]phosgene using a carbon tetrachloride detection tube kit in environmental air analysis and the automated synthesis system for preparing [¹¹C]phosgene have been developed in 2009. This apparatus has been used for routine synthesis of ¹¹C-labeled tracers 1-4 times/week. Using [¹¹C]phosgene we have developed and produced many PET radiotracers containing [¹¹C]urea and [¹¹C]carbamate moieties. In this review, we report the performance of our method for preparing [¹¹C]phosgene, including automated synthesis apparatus developed in house, and the application of [¹¹C]phosgene for development and production of ¹¹C-labeled PET tracers.