title: Syntheses and radiosyntheses of two carbon-11 labeled potent and selective radioligands for imaging vesicular acetylcholine transporter.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA.
authors.forename: Prashanth K
authors.initials: PK
authors.lastname: Padakanti
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Parsons
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D050494:Vesicular Acetylcholine Transport Proteins