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

α,ß-aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short-lived (t1/2=20.3 min), ß+-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,ß-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.

A conforming auxiliary space preconditioner for the mass conserving stress-yielding method.

We are studying the efficient solution of the system of linear equations stemming from the mass conserving stress-yielding (MCS) discretization of the Stokes equations. We perform static condensation to arrive at a system for the pressure and velocity unknowns. An auxiliary space preconditioner for the positive definite velocity block makes use of efficient and scalable solvers for conforming Finite Element spaces of low order and is analyzed with emphasis placed on robustness in the polynomial degree of the discretization. Numerical experiments demonstrate the potential of this approach and the efficiency of the implementation.