Facile and rapid one-step radiosynthesis of [(18)F]BAY94-9172 with a new precursor

[(18)F]BAY94-9172 (Florbetaben) (Compound 8) is a positron emission tomography (PET) tracer that is currently in Phase III study for in vivo mapping of fibrillar amyloid β as a pathological hallmark for Alzheimer's disease. This work reports new methods for the synthesis of [(19)F]BAY94-9172 and its two different precursors and radiosynthesis of [(18)F]BAY94-9172 with the two precursors by purification using Sep-Pak cartridge.

The reference standard [(19)F]BAY94-9172 and the new precursor (Compound 9) were obtained from the reactions of (E)-4-methylamino-4'-hydroxystilbene (Compound 1) with methanesulfonic acid 2-[2-(2-fluoro-ethoxy)-ethoxy]-ethyl ester (Compound 11) and methanesulfonic acid 2-[2-(2-methanesulfonyloxy-ethoxy)-ethoxy]-ethyl ester (Compound 13), respectively. The reported precursor (Compound 6) is an N-BOC-protected mesylate compound, which was obtained from Compound 9. The one-step radiosynthesis of [(18)F]BAY94-9172 was carried out in the modified PET-MF-2V-IT-1 synthesizer by [(18)F]fluorination of the new precursor (Compound 9) and purification with plus C18 Sep-Pak cartridges and was compared with two-step one-pot radiosynthesis using the reported precursor (Compound 6) and Sep-Pak cartridge purification.

For one-step radiosynthesis, the uncorrected radiochemical yield of [(18)F]BAY94-9172 was 23 ± 3% (n = 5, based on [(18)F]fluoride) within 30 min and the radiochemical purity was greater than 95%. For two-step one-pot radiosynthesis, the uncorrected radiochemical yield of [(18)F]BAY94-9172 was 17 ± 2% in 45 min (n = 4, based on [(18)F]fluoride) with the radiochemical purity being above 95% after the Sep-Pak cartridge purification.

[(19)F]BAY94-9172 and the two precursors were synthesized by a short synthetic route. Compared with HPLC purification, the use of Sep-Pak purification of [(18)F]BAY94-9172 reduced the total radiosynthesis time. The one-step radiosynthesis of [(18)F]BAY94-9172 is convenient and can easily be applied to the commercial PET tracer synthesizer for automated synthesis.