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. 2024 May 17;30(28):e202400581.
doi: 10.1002/chem.202400581. Epub 2024 Apr 4.

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

Marius Ozenil  1 , Lukas Kogler  2   3 , Braeden A Mair  4   5 , Marcus Hacker  1 , Wolfgang Wadsak  1   3 , Benjamin H Rotstein  4   5   6 , Verena Pichler  2
Affiliations

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

Marius Ozenil et al. Chemistry. .

Abstract

α,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.

Keywords: PARP; PET tracer; carbon-11.

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