Intramolecular Friedel‐Crafts Acylation of [11C]Isocyanates Enabling the Radiolabeling of [carbonyl‐11C]DPQ

Abstract

Abstractα,β‐aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short‐lived (t1/2=20.3 min), β+‐decaying carbon‐11, which has prevented their application as positron emission tomography tracers. Herein, we developed, optimized, and applied a widely applicable, one‐pot, quick, robust and automatable radiolabeling method for α,β‐aromatic lactams starting from [11C]CO2 using the reagent POCl3⋅AlCl3. This method proceeds via intramolecular Friedel‐Crafts acylation of in situ formed [11C]isocyanates and shows a broad substrate scope for the formation of five‐ and six‐membered rings. We implemented our developed labeling method for the radiosynthesis of the potential PARP1 PET tracer [carbonyl‐11C]DPQ in a clinical radiotracer production facility following the standards of the European Pharmacopoeia.