Radiosynthesis of a Carbon-11 Labeled PDE5 Inhibitor [11C]TPN171 As a New Potential PET Heart Imaging Agent

To develop PET tracers for imaging of heart disease, a new carbon-11 labeled potent and selective PDE5 inhibitor [11C]TPN171 ([11C]9) has been synthesized. The reference standard TPN171 (9) and its corresponding precursor desmethyl-TPN171 (11) were synthesized from methyl 3-oxovalerate and 2-hydroxybenzonitrile in 9 and 10 steps with 31% and 25% overall chemical yield, respectively. The radiotracer [11C]TPN171 was prepared from desmethyl-TPN171 with [11C]CH3OTf through N-11C-methylation and isolated by HPLC purification followed by SPE formulation in 45–55% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was in a range of 370–740 GBq/μmol.