Facile automated synthesis of [¹⁸F]fluoromethyl-d₂ group in a commercial ¹⁸F-synthetic module

Objectives In our recent study, we demonstrated that ¹⁸F-fluoromethyl ether group could be used the convenient application for radiofluorination of ¹¹C-radiotracer containing a methoxy group. For the routine application of biologically active compound, a fully automated synthesis was developed by radiofluorination of the prosthetic group (¹⁸F-CD₂BrF), followed by O-alkylation in the commercially available ¹⁸F-synthetic module.

Methods A TRACERlab FX N Pro chemistry module containing two reactors was used after a little modification. The position of tubing lines and valves were modified to enable for bubbling of ¹⁸F-CD₂BrF into the second reactor. The flow control regulator was installed for control of bubbling rate and C18 environmental Sep-Pak cartridge was introduced for separation between CD₂Br₂ and ¹⁸F-CD₂BrF. The air compressor line for cooling of reactor was connected with coiled copper line (1/4 inch) which was immersed the cooling bath of -50 ^oC. After separation of ¹⁸F-CD₂BrF, we attempt the synthesis of ¹⁸F-fluoromethyl-d₂ substituted PBR28 ([¹⁸F]1), TSPO selective radioligand, as previously reported by our group.

Results The reactive gas-type ¹⁸F-CD₂BrF was prepared from CD₂Br₂ with about 50% of radiolabeling yield. After distillation, the trapped ¹⁸F-CD₂BrF into the second reactor was around 10% based on the initial radioactivity of fluorine-18. After alkylation of desmethyl-PBR28, the overall radiochemical yield was 5.4±0.8% (n.d.c.) with 99% of radiochemical purity. The specific activity of [¹⁸F]1 was over 266 GBq/μmol. Total automated production time needs about 80 min including HPLC purification.

Conclusions A fully automated module for the introduction of ¹⁸F-fluoromethyl-d₂ group was successfully developed through modifying the current module. This optimized condition could be applied to various ¹⁸F-labeled radiopharmaceuticals.