Synthesis of [18F]SiFB: a prosthetic group for direct protein radiolabeling for application in positron emission tomography

N-Succinimidyl 3-(di-tert-butyl[F-18]fluorosilyl)benzoate ([F-18]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-[F-18]fluorobenzoate ([F-18]SFB), the 'gold-standard' prosthetic group for protein F-18-labeling, but can be synthesized using a much shorter and technically easier procedure. A recently reported simple procedure to obtain anhydrous F-18- 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 [F-18]SiFB. The labeling of [F-18]SiFB is performed by a fast F-18-F-19 isotopic exchange (IE) reaction at room temperature (20-25 degrees C) within 30 min. [F-18]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 mu mol(-1) (> 500 Ci mmol(-1)) can be obtained. Finally, incubation of [F-18]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.