title: Synthesis of p-(di-tert-butyl[(18)F]fluorosilyl)benzaldehyde ([(18)F]SiFA-A) with high specific activity by isotopic exchange: a convenient labeling synthon for the (18)F-labeling of N-amino-oxy derivatized peptides.
abstract: The syntheses of different (18)F-labeled peptides using the highly effective labeling synthon p-(di- tert-butylfluorosilyl) benzaldehyde ([ (18)F]SiFA-A) for the development of (18)F-radiopharmaceuticals for oncological positron emission tomography (PET) is reported. The novel and mild labeling technique for the radiosynthesis of [ (18)F]SiFA-A, based on an unexpectedly efficient isotopic (19)F- (18)F exchange, yielded the (18)F-synthon [ (18)F]SiFA-A in almost quantitative yields in high specific activities between 225 and 680 GBq/micromol (6081-18 378 Ci/mmol) without applying HPLC purification. The [ (18)F]SiFA-A was finally used to label the N-terminal amino-oxy (N-AO) derivatized peptides AO-Tyr (3)-octreotate (AO-TATE), cyclo(fK(AO-N)RGD and N-AO-PEG 2-[D-Tyr-Gln-Trp-Ala-Val-betaAla-His-Thi-Nle-NH 2] (AO-BZH3, a bombesin derivative) in high radiochemical yields. Density functional theory (DFT) calculations confirmed high efficiency of the isotopic exchange, which is predicted to proceed via a pentacoordinate siliconate intermediate dissociating immediately to form the radiolabeled [ (18)F]SiFA-A.
authors.affiliation: Lady Davis Institute, Jewish General Hospital, and Montreal Neurological Institute, McGill University, Montreal, Canada. esther.schirrmacher@mcgill.ca
authors.forename: Esther
authors.initials: E
authors.lastname: Schirrmacher
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.forename: Marek
authors.initials: M
authors.lastname: Cypryk
authors.forename: Gerrit
authors.initials: G
authors.lastname: Bradtmöller
authors.forename: Martin
authors.initials: M
authors.lastname: Schäfer
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Klaus
authors.initials: K
authors.lastname: Jurkschat
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D000586:Amination; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D005462:Fluorine Radioisotopes; D017646:Organosilicon Compounds; D010455:Peptides; D019275:Radiopharmaceuticals; C525968:p-(di-tert-butyl((18)F)fluorosilyl)benzaldehyde