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

Nat Protoc. 2012 Nov;7(11):1956-63. doi: 10.1038/nprot.2012.110. Epub 2012 Oct 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Halogenation
  • Isotope Labeling / methods*
  • Organosilicon Compounds / chemical synthesis*
  • Oxalic Acid / chemistry
  • Positron-Emission Tomography / methods*
  • Proteins / analysis
  • Proteins / chemistry
  • Succinimides / chemical synthesis*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • N-succinimidyl 3-(di-tert-butylfluorosilyl)benzoate
  • Organosilicon Compounds
  • Proteins
  • Succinimides
  • cryptating agent 222
  • Oxalic Acid