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

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 have more recently enabled the direct radiolabeling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop-based system employed 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 non-isolated radiochemical yield of 72% (decay corrected) within just 3 min 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 labeled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for GMP production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.