The development of C-carbonylation chemistry: A systematic view.

The prospects for using carbon-11 labelled compounds in molecular imaging has improved with the development of diverse synthesis methods, including C-carbonylations and refined techniques to handle [C]carbon monoxide at a nanomole scale. Facilitating biological research and molecular imaging was the driving force when [C]carbon monoxide was used in the first in vivo application with carbon-11 in human (1945) and when [C]carbon monoxide was used for the first time as a chemical reagent in the synthesis of [C]phosgene (1978). This review examines a rich plethora of labelled compounds synthesized from [C]carbon monoxide, their chemistry and use in molecular imaging. While the strong development of the C-carbonylation chemistry has expanded the carbon-11 domain considerably, it could be argued that the number of C-carbonyl compounds entering biological investigations should be higher. The reason for this may partly be the lack of commercially available synthesis instruments designed for C-carbonylations. But as this review shows, novel and greatly simplified methods to handle [C]carbon monoxide have been developed. The next important challenge is to make full use of these technologies and synthesis methods in PET research. When there is a PET-tracer that meets a more general need, the incentive to implement C-carbonylation protocols will increase.