Labeling proteins with fluorine-18 using N-succinimidyl 4-[ 18F]fluorobenzoate

Abstract

Two methods were investigated for the no-carrier-added synthesis of N-succinimidyl 4-[ 18F]fluorobenzoate (S[ 18F]FB). The first, an attempted nucleophilic aromatic substitution by [ 18F]fluoride on N-succinimidyl 4-nitrobenzoate was unsuccessful. The second method involved three steps; [ 18F]fluoride for trimethylammonium substitution on 4-formyl- N,N,N-trimethylanilinium triflate, oxidation to 4-[ 18F]fluorobenzoic acid, followed by reaction with N-hydroxysuccinimide and dicyclohexylcarbodiimide to form S[ 18F]FB. Total synthesis and purification time was 100 min and the overall radiochemical yield was 25% (decay corrected). A monoclonal antibody F(ab′) 2 fragment could be labeled in 40–60% yield by reaction with S[ 18F]FB for 15–20 min. The tissue distribution in normal mice and in vitro tumor binding of the antibody F(ab′) 2 labeled by reaction with S[ 18F]FB were comparable to those observed for the fragment after radioiodination using N-succinimidyl 4-[ 125I]iodobenzoate.