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

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