In this work, a mild and effective method is described for the [11C]-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions, which could facilitate positron emission tomography studies with such biomolecules. The presented method relies on the use of specific biphosphine palladium–methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [11C]carbon monoxide. The protocol facilitates the production of native N-11C-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides.

The chemistry presented in this paper represents one of the many exciting projects that are currently ongoing in our Carbon Dioxide Activation Center (CADIAC) at the Interdisciplinary Nanoscience Center and the Department of Chemistry, Faculty of Natural Sciences, Aarhus University, which is financed by the Danish National Research Foundation. The project was only possible because of the tremendous efforts of two talented PhD students, Thomas L. Andersen and Heidi F. Christoffersen, and a  great collaboration with Dr. Hélène Audrain at the Department of Nuclear Medicine and PET Center, Aarhus University Hospital, and Dr. Gunnar Antoni and Patrik Nordmann from the Department of Medicinal Chemistry, Uppsala University.