title: Oxalic acid supported Si-18F-radiofluorination: one-step radiosynthesis of N-succinimidyl 3-(di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for protein labeling.
abstract: N-Succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB), a novel synthon for one-step labeling of proteins, was synthesized via a simple (18)F-(19)F isotopic exchange. A new labeling technique that circumvents the cleavage of the highly reactive active ester moiety under regular basic (18)F-labeling conditions was established. In order to synthesize high radioactivity amounts of [(18)F]SiFB, it was crucial to partially neutralize the potassium oxalate/hydroxide that was used to elute (18)F(-) from the QMA cartridge with oxalic acid to prevent decomposition of the active ester moiety. Purification of [(18)F]SiFB was performed by simple solid-phase extraction, which avoided time-consuming HPLC and yielded high specific activities of at least 525 Ci/mmol and radiochemical yields of 40-56%. In addition to conventional azeotropic drying of (18)F(-) in the presence of [K(+)⊂2.2.2.]C(2)O(4), a strong anion-exchange (SAX) cartridge was used to prepare anhydrous (18)F(-) for nucleophilic radio-fluorination omitting the vacuum assisted drying of (18)F(-). Using a lyophilized mixture of [K(+)⊂2.2.2.]OH resolubilized in acetonitrile, the (18)F(-) was eluted from the SAX cartridge and used directly for the [(18)F]SiFB synthesis. [(18)F]SiFB was applied to the labeling of various proteins in likeness to the most commonly used labeling synthon in protein labeling, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Rat serum albumin (RSA), apo-transferrin, a β-cell-specific single chain antibody, and erythropoietin were successfully labeled with [(18)F]SiFB in good radiochemical yields between 19% and 36%. [(18)F]SiFB- and [(18)F]SFB-derivatized RSA were directly compared as blood pool imaging agents in healthy rats using small animal positron emission tomography. Both compounds demonstrated identical biodistributions in healthy rats, accurately visualizing the blood pool with PET.
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University , Montreal, QC, Canada. alexey.kostikov@mcgill.ca
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: Sabrina
authors.initials: S
authors.lastname: Niedermoser
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Kovacevic
authors.forename: Antonio
authors.initials: A
authors.lastname: Aliaga
authors.forename: Klaus
authors.initials: K
authors.lastname: Jurkschat
authors.forename: Bjoern
authors.initials: B
authors.lastname: Wängler
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004921:Erythropoietin / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D019815:Oxalic Acid / Q000737:chemistry*; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry; D012825:Silicon / Q000737:chemistry*; D057127:Single-Chain Antibodies / Q000737:chemistry; D052616:Solid Phase Extraction; D013194:Staining and Labeling / Q000379:methods*; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry
chemical_list: D001059:Apoproteins; D005462:Fluorine Radioisotopes; C572729:N-succinimidyl 3-(di-tert-butylfluorosilyl)benzoate; D017646:Organosilicon Compounds; D012709:Serum Albumin; D057127:Single-Chain Antibodies; D013388:Succinimides; D014168:Transferrin; C028284:apotransferrin; D004921:Erythropoietin; D019815:Oxalic Acid; D012825:Silicon