In-loop flow [11C]CO2 fixation and radiosynthesis of N,N′-[11C]dibenzylurea

Article abstract of DOI:10.1002/jlcr.3568

Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([¹¹C]CO₂), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [¹¹C]CO₂ fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [¹¹C]CO₂, and the advantages afforded by the use of a loop-based system used in ¹¹C-methylation and ¹¹C-carboxylation reactions inspired us to apply the [¹¹C]CO₂ fixation “in-loop.” In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [¹¹C]CO₂ fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [¹¹C]CO₂ using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N′-[¹¹C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3?minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [¹¹C]CO₂ fixation can be achieved in a low-volume (150?μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11–labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [¹¹C]CO₂ trapping/fixation reactions for the production of PET radiotracers.