[11C]CO2 BOP fixation with amines to access 11C-labeled ureas for PET imaging

Carbon-11 (¹¹C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half-life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high-yielding synthesis methods is crucial for the application of ¹¹C-labeled tracers in humans.

In this study, we present a novel and efficient method for the reaction of [¹¹C]CO₂ with amine precursors using benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP) to access ¹¹C-labeled ureas. Our method is extremely fast as it only requires transfer of [¹¹C]CO₂ into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired ¹¹C-labeled urea. This simple procedure makes it possible to radiolabel urea directly from [¹¹C]CO₂ without the need for advanced equipment, making the method applicable for all laboratories where [¹¹C]CO₂ is available. We synthesized a small series of aliphatic symmetrical and non-symmetrical ¹¹C-labeled ureas using this method, and achieved good to excellent yields.

The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [¹¹C]CO₂, facilitating its reaction with amines to obtain ¹¹C-labeled ureas.