title: Synthesis of [(18)F]SiFB: a prosthetic group for direct protein radiolabeling for application in positron emission tomography.
abstract: N-Succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) is a highly reactive prosthetic group for radiolabeling of proteins for use in positron emission tomography (PET). It is similar to N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB), the 'gold-standard' prosthetic group for protein (18)F-labeling, but can be synthesized using a much shorter and technically easier procedure. A recently reported simple procedure to obtain anhydrous (18)F- by avoiding time-consuming azeotropic drying is applied with a slight modification to prevent basic hydrolysis of the active N-hydroxysuccinimide (NHS) ester moiety of [(18)F]SiFB. The labeling of [(18)F]SiFB is performed by a fast (18)F-(19)F isotopic exchange (IE) reaction at room temperature (20-25 °C) within 30 min. [(18)F]SiFB is purified using a C18 cartridge instead of HPLC, further decreasing the overall time required for protein labeling. High specific activities > 18.5 GBq μmol(-1) (> 500 Ci mmol(-1)) can be obtained. Finally, incubation of [(18)F]SiFB with the desired protein in an aqueous solution at pH 9, followed by HPLC purification, provides the final solution of the labeled protein ready for in vivo applications.
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Alexey P
authors.initials: AP
authors.lastname: Kostikov
authors.forename: Joshua
authors.initials: J
authors.lastname: Chin
authors.forename: Katy
authors.initials: K
authors.lastname: Orchowski
authors.forename: Esther
authors.initials: E
authors.lastname: Schirrmacher
authors.forename: Sabrina
authors.initials: S
authors.lastname: Niedermoser
authors.forename: Klaus
authors.initials: K
authors.lastname: Jurkschat
authors.forename: Liuba
authors.initials: L
authors.lastname: Iovkova-Berends
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D054879:Halogenation; D007553:Isotope Labeling / Q000379:methods*; D017646:Organosilicon Compounds / Q000138:chemical synthesis*; D019815:Oxalic Acid / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D011506:Proteins / Q000032:analysis / Q000737:chemistry; D013388:Succinimides / Q000138:chemical synthesis*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C572729:N-succinimidyl 3-(di-tert-butylfluorosilyl)benzoate; D017646:Organosilicon Compounds; D011506:Proteins; D013388:Succinimides; C006071:cryptating agent 222; D019815:Oxalic Acid