title: A combined simple bubbling method with high performance liquid chromatography purification strategy, higher radiochemical yield and purity and faster preparation of carbon-11-raclopride.
abstract: OBJECTIVE
  Carbon-11-raclopride (¹¹C-R) is a positron-emitting radiotracer successfully used for the study of cognitive control and widely applied in PET imaging. A simple automated preparation of ¹¹C-R by using the reaction of carbon-(11)-methyl triflate (¹¹C-MeOTF) or ¹¹C-methyl iodide (¹¹C-MeI) with demethylraclopride is described.
  
  
  METHODS
  Specifically we used a simple setup applied an additional "U" reaction vessel for ¹¹C-MeOTf compared with ¹¹C-MeI and assessed the influence of several solvents and of the amount of the percussor for ¹¹C-methylation of demethylraclopride by the bubbling method. The reversal of retention order between product and its precursor has been achieved for ¹¹C-R, enabling collection of the purified ¹¹C-R by using the HPLC column after shorter retention time.
  
  
  RESULTS
  By the improved radiosynthesis and purification strategy, ¹¹C-R could be prepared with higher radiochemical yield than that of the previous studies. The yield for ¹¹C-MeOTf was 76% and for ¹¹C-CH3I >26% and with better radiochemical purity (>99% based on both ¹¹C-MeOTf and ¹¹C-MeI) as compared to the previously obtained purity of ¹¹C-R using HPLC method with acetonitrile as a part of mobile phase. Furthermore, by using ethanol as the organic modifier, residual solvent analysis prior to human injection could be avoided and ¹¹C-R could be injected directly following simple dilution and sterile filtration.
  
  
  CONCLUSIONS
  Improved radiosynthesis and HPLC purification in combination with ethanol containing eluent, extremely shortened the time for preparation of ¹¹C-R, gave a higher radiochemical yield and purity for ¹¹C-R and can be used for multiple and faster synthesis of ¹¹C-R and probably for other ¹¹C-labeled radiopharmaceuticals.
authors.affiliation: Department of Nuclear Medicine, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang, P.R.China. Loucen126@126.com.
authors.forename: Huacheng
authors.initials: H
authors.lastname: Huang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ning
authors.forename: Bucheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Cen
authors.initials: C
authors.lastname: Lou
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control; D007553:Isotope Labeling / Q000379:methods*; D008422:Materials Testing; D020891:Raclopride / Q000138:chemical synthesis* / Q000302:isolation & purification*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification*
chemical_list: D019275:Radiopharmaceuticals; D020891:Raclopride