Efficient ¹¹C‑Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis

Abstract

We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with ¹¹CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first ¹¹C-carbonyl labeling of an approved PET tracer, [¹¹C]­raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [¹¹C]­olaparib and [¹¹C]­JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other ¹¹C-labeling strategies