Improved synthesis of N-succinimidyl 4-[18F]fluorobenzoate and its application to the labeling of a monoclonal antibody fragment

Bioconjug Chem. 1994 Jul-Aug;5(4):352-6. doi: 10.1021/bc00028a012.


Our previously reported method for the 18F labeling of antibodies using N-succinimidyl 4-[18F]fluorobenzoate (SFB) involved a rather long synthesis time. Here we present an improved method for the synthesis of SFB which reduces the synthesis time by about 45 min. A reaction time of 5-8 min (versus 25 min for the original procedure) was sufficient in the fluorination step to form 4-[18F]fluorobenzaldehyde in high yield. In the original method, 30-35 min was necessary to convert 4-[18F]fluorobenzoic acid to SFB using dicyclohexylcarbodiimide and N-hydroxysuccinimide. When N,N'-disuccinimidyl carbonate was used, facile conversion of 4-fluorobenzoic acid to SFB was seen at a micromolar level. At a tracer level, no product was formed at room temperature; however, complete consumption of starting material was observed. Heating at 150 degrees C resulted in the formation of SFB in more than 80% yield in 1-3 min. HPLC purification of SFB was necessary since use of crude SFB, or SFB purified using a silica solid-phase cartridge column, resulted in lower protein coupling yields. Furthermore, use of crude SFB resulted in cross-linking and lower immunoreactivity of antibody. Largely as a result of the considerable reduction in total labeling time, these modifications have increased the amount of 18F-labeled antibody available per 100 mCi of [18F]fluoride by 30-35%.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / pharmacology
  • Benzoates / chemical synthesis*
  • Benzoates / pharmacokinetics
  • Benzoates / pharmacology
  • Chromatography, High Pressure Liquid
  • Fluorine Radioisotopes / chemistry
  • Indicators and Reagents
  • Isotope Labeling
  • Mice
  • Spectrophotometry, Ultraviolet
  • Succinimides / chemical synthesis*
  • Succinimides / pharmacokinetics
  • Succinimides / pharmacology
  • Tissue Distribution
  • Tomography, Emission-Computed


  • Antibodies, Monoclonal
  • Benzoates
  • Fluorine Radioisotopes
  • Indicators and Reagents
  • Succinimides
  • N-succinimidyl-4-fluorobenzoate