Radiosynthesis of carbon-11 labeled PDE5 inhibitors as new potential PET radiotracers for imaging of Alzheimer's disease

To develop PET tracers for imaging of Alzheimer's disease, new carbon-11 labeled potent and selective PDE5 inhibitors have been synthesized. The reference standards (5) and (12), and their corresponding desmethylated precursors (6) and (13) were synthesized from methyl 2-amino-5-bromobenzoate and (4-methoxyphenyl)methanamine in multiple steps with 2%, 1%, 1% and 0.2% overall chemical yield, respectively. The radiotracers ([C-11]5) and ([C-11]12) were prepared from their corresponding precursors 6 and 13 with [C-11]CH3OTf through O-C-11-methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [C-11]CO2 and decay corrected to EOB. The radiochemical purity was > 99%, and the molar activity (A(m)) at EOB was in a range of 370-740 GBq/mol.