INTRODUCTION: [(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. METHODS: 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. RESULTS: 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. CONCLUSION: [(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.
INTRODUCTION: [(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. METHODS: 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. RESULTS: 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. CONCLUSION: [(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.
Authors: Ksenia Lisova; Jia Wang; Tibor Jacob Hajagos; Yingqing Lu; Alexander Hsiao; Arkadij Elizarov; R Michael van Dam Journal: Sci Rep Date: 2021-10-19 Impact factor: 4.379
Authors: Aisling M Chaney; Francisco R Lopez-Picon; Sophie Serrière; Rui Wang; Daniela Bochicchio; Samuel D Webb; Matthias Vandesquille; Michael K Harte; Christina Georgiadou; Catherine Lawrence; Julie Busson; Johnny Vercouillie; Clovis Tauber; Frédéric Buron; Sylvain Routier; Tristan Reekie; Anniina Snellman; Michael Kassiou; Johanna Rokka; Karen E Davies; Juha O Rinne; Dervis A Salih; Frances A Edwards; Llwyd D Orton; Stephen R Williams; Sylvie Chalon; Hervé Boutin Journal: Theranostics Date: 2021-05-03 Impact factor: 11.556
Authors: Behrooz H Yousefi; Boris von Reutern; Daniela Scherübl; André Manook; Markus Schwaiger; Timo Grimmer; Gjermund Henriksen; Stefan Förster; Alexander Drzezga; Hans-Jürgen Wester Journal: EJNMMI Res Date: 2015-03-28 Impact factor: 3.138