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 [C-11]CO2 fixation chemistry. [C-11]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [C-11]CO2/intramolecular cyclization; [C-11]-tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [C-11]CO2 followed by an intermolecular cycloaddition between a [C-11]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [C-11]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [C-11]acrylic acid (generated from [C-11]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 [C-11]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.