Automated radiosynthesis of [11C]CH3Br as a new radioprecursor for methylation reaction

Objectives [11C]CH3I as a most widely used methylating agent for synthesis of a majority of 11C-labelled positron emission tomography (PET) radiotracers, especially in the area of receptor imaging, is commonly produced by “wet” method and “gas phase” method . Due to the complexity of the gas phase method, a simple automated synthesis of [11C]CH3Br as a new methylating agent produced by the most widely used wet method is described in this work. Also, preparation of L- [S-methyl-11C]methionine(MET), L-[S-methyl-11C]cysteine(CYS) as a new tumor tracer, [N-methyl-11C]choline(CH), and [11C]-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane(CFT) with [11C]CH3Br is reported.

Methods [11C]CH3Br was produced following three steps: (i) reduction of [11C]CO2 with lithiumaluminumhydride (LiAlH4) solution; (ii) treatment with hydrobromic acid (HBr); and (iii) distillation of [11C]CH3Br under continuous flow of an inert gas. [11C]Methylation of L-homocysteine thiolactone hydrochloride, L-cysteine, 2-dimethylaminoethanol, and nor-β-CFT as precursors with [11C]CH3Br and purification with Sep-Pak cartridges gave MET, CYS, CH, and CFT, respectively.

Results The uncorrected radiochemical yield of [11C]CH3Br was about 36% based on [11C]CO2 within a total synthesis time of 10 min and the purity of [11C]CH3Br was greater than 95%. The uncorrected yields of MET, CYS, CH, and CFT were 70%, 70%, 60%, and 50% based on [11C]CH3Br within a total synthesis time of 2 min, 2 min, 5min, and 8 min, respectively.

Conclusions [11C]CH3Br is a good radioprecursor for [11C]methylation reaction to produce 11C-labelled tracers. CYS as a MET analogue can be prepared by on-column methylation with [11C]CH3Br. A good yield of CFT can be obtained by [11C]methylation with [11CH3]triflate from [11C]CH3Br and purification with Sep-Pak C18 cartridge.

Research Support NDFC(No.30970856), 863 Program (No. 2008AA02Z430), SYSU (No. 80000-3126132)