Automated Synthesis of (S-[~(11)C]-methyl)-L-methionine and (S-[~(11)C]-methyl)-L-cysteine by On-column [~(11)C]methylation

After~(11)CO_2 is produced via nuclear reaction~(14)N(p,α)~(11)C at a PET trace cyclotron,~(11)CH_3I is synthesized from the hydrogenation of~(11)CO_2 by catalyst Ni and the recycle iodination of~(11)C-CH_4 at~(11)CH_3I Micro Lab Process Module, with uncorrected radiochemical yield more than 30% in the synthesis time about 12 min. (S-[~(11)C]-methyl)-L-methionine (~(11)C-MET) is synthesized from [~(11)C]methylation of~(11)CH_3I with precursor L-homocysteine thiolactone hydrochloride in NaOH solution on a commercial C18 Sep-Pak Plus cartridge as a solid-phase support material at the semi-automated system for the synthesis of~(11)C-MET. The corrected radiochemical yield of [(~(11)C)]methylation is more than 85% with the synthesis time about 6 min, the radiochemical purity of~(11)C-MET is above 99%, and the enantiomeric purity is about 90%. (S-[(~(11)C)]-methyl)-L-cysteine ((~(11)C)-CYS) is synthesized from [(~(11)C)] methylation of(~(11)CH_3I) with precursor L-cysteine on a commercial cartridge as a solid-phase support material at the PET-CS-I model fully automated system. The uncorrected radiochemical yield of~(11)C-CYS from~(11)CH_3I is more than 50% with the synthesis time about 2 min, the radiochemical purity of~(11)C-CYS is above 99%, and the enantiomeric purity is over 90%. The synthetic~(11)C-MET and~(11)C-CYS injections can be suitable for preclinical and clinical study with PET imaging.