Synthesis of Diverse ¹¹C‑Labeled PET Radiotracers via Direct Incorporation of [¹¹C]CO₂

Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [¹¹C]­CO₂ fixation chemistry. [¹¹C]­QZ (glutaminyl cyclase) was prepared via a tandem trapping of [¹¹C]­CO₂/intramolecular cyclization; [¹¹C]­tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [¹¹C]­CO₂ followed by an intermolecular cycloaddition between a [¹¹C]­isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [¹¹C]­ibrutinib (Bruton’s tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [¹¹C]­acrylic acid (generated from [¹¹C]­CO₂ fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1–5% radiochemical yield (noncorrected, based upon [¹¹C]­CO₂). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported