Syntheses and radiosyntheses of two carbon-11 labeled potent and selective radioligands for imaging vesicular acetylcholine transporter.

ABSTRACT

PURPOSE: The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. The syntheses and C-11 labeling of two potent enantiopure VAChT inhibitors are reported here. PROCEDURES Two VAChT inhibitors, (±)-2 and (±)-6, were successfully synthesized. A chiral HPLC column was used to resolve the enantiomers from each corresponding racemic mixture for in vitro characterization. The radiosyntheses of (-)-[(11)C]2 and (-)-[(11)C]6 from the corresponding desmethyl phenol precursor was accomplished using [(11)C]methyl iodide or [(11)C]methyl triflate, respectively. RESULTS: The synthesis of (-)-[(11)C]2 was accomplished with 40-50 % radiochemical yield (decay-corrected), SA > 480 GBq/µmol (EOB), and radiochemical purity >99 %. Synthesis of (-)-[(11)C]6 was accomplished with 5-10 % yield, SA > 140 GBq/µmol (EOB), and radiochemical purity >97 %. The radiosynthesis and dose formulation of each tracer was completed in 55-60 min. CONCLUSIONS: Two potent enantiopure VAChT ligands were synthesized and (11)C-labeled with good radiochemical yield and specific activity.