Evaluation of base-free C-11-Raclopride synthesis with various solvents

2501 Objectives [11C]Raclopride is usually synthesized using base such as NaH, NaOH or K2CO3 in many radiochemistry labs. We evaluated a possibility of six different solvents for [11C]raclopride synthesis without base; DMF, DMSO, EtOH, 2-butanone (MEK), MeCN, or cyclohexanone (c-HXO). We also tried to improve synthesis method using optimal solvent. Methods [11C]MeI and [11C]MeOTf were produced by a gas-phase method using TRACERlab FXC Pro. O-desmethylraclopride (1 mg, 3 umol) in 100 uL of each solvent, DMF or DMSO for [11C]MeI and MeCN, EtOH ,MEK or c-HXO for [11C]MeOTf, were loaded into HPLC loop. After purging with methylating agents for 3 min at RT, the reaction mixture was purified by HPLC system. To compare the production yield, we performed the vial synthesis method with 200 uL of precursor solution at 80℃, 5 min. Results The radiochemical yield of [11C]raclopride was 5.8 %, 2.8% or 7.3% with MeCN, MEK or c-HXO as a solvent without decay correction (EOS), respectively, and we could not find the product peak from HPLC using DMF, DMSO or EtOH. Out of MeCN, MEK and c-HXO, c-HXO showed the highest radiolabeling yield for the loop method. The radiolabeling yield of the vial method at 80℃ using c-HXO was 30.0 % (n=3) without decay correction (EOS). Conclusions We confirmed that [11C]raclopride could be synthesized without any base, and c-HXO was the optimal solvent for [11C]raclopride synthesis.