Syntheses and Radiosyntheses of Two Carbon-11 Labeled Potent and Selective Radioligands for Imaging Vesicular Acetylcholine Transporter

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 (−)-[¹¹C]2 and (−)-[¹¹C]6 from the corresponding desmethyl phenol precursor was accomplished using [¹¹C]methyl iodide or [¹¹C]methyl triflate, respectively.

Results: The synthesis of (−)-[¹¹C]2 was accomplished with 40–50 % radiochemical yield (decay-corrected), SA > 480 GBq/μmol (EOB), and radiochemical purity >99 %. Synthesis of (−)-[¹¹C]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 ¹¹C-labeled with good radiochemical yield and specific activity.