Hélène Audrain, April 2016

The application of PET imaging has expanded considerably over the last few years, and hence it is crucial that reliable and efficient methods are available for the isotopic labelling of pharmaceutically relevant molecules. This includes methods for handling the radioactive starting materials delivered from the cyclotron, as well as the adaptation of new chemical techniques to PET chemistry.
As a part of our research activities, we have focused our efforts on the use of C-11 carbon monoxide as a means to introduce carbon-11 in structurally challenging molecules applying palladium-catalyzed carbonylations. The adaptation of this carbonylation chemistry is complementary to the more common methylation reactions with C-11 methyl iodide and methyl triflate, and therefore increases the portfolio of the possible radiotracers that can be produced at our PET-Center.
To exploit palladium-catalyzed carbonylations reactions to a PET setting, some adjustments are required to tame the C11-CO coming from the cyclotron. Our first challenge was to develop a simple and efficient low pressure setup for the trapping and release of C-11 CO. Our “homemade” device was successfully applied to the last-step C11-labelling of biomolecule-based substrates, a project carried out in collaboration with the team of Philippe Hermange at the University of Bordeaux (Thomas Cornilleau’s reference)

Secondly, thanks to a collaboration with the groups of Prof. Troels Skrydstrup from the Interdisciplinary Nanoscience Center and Department of Chemistry at Aarhus University, Denmark, and Dr. Gunnar Antoni from the Preclinical PET Platform at the University of Uppsala, Sweden, we have developed a novel strategy for the introduction of C11-carbonyl functional groups into structurally demanding molecules. This was accomplished via the direct aminocarbonylation of aryl palladium complexes allowing access to [11C]raclopride, [11C]-JNJ, [11C]olaparib. (Thomas Andersen’s reference)

References:

Thomas Cornilleau et al, ”General Last-Step Labeling of Biomolecule-Based Substrates by [¹²C], [¹³C], and [¹¹C] Carbon Monoxide”, Org. Lett., 2015, 17 (2), pp 354–357.

Thomas L. Andersen et al. ”Efficient 11C-Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis”, J. Am. Chem. Soc., 2015, 137 (4), pp 1548–1555