Synthesis of N-succinimidyl 4-[18F]fluorobenzoate, an agent for labeling proteins and peptides with 18F

This protocol describes the step-by-step procedure for the synthesis of N-succinimidyl 4-18F]fluorobenzoate (18F]SFB), an agent widely used for labeling proteins and peptides with the positron-emitting radionuclide 18F. The protocols for the synthesis of unlabeled SFB and the quaternary salt precursor 4-formyl-N,N,N-trimethyl benzenaminium trifluoromethane sulfonate also are described. For the 18F]SFB synthesis, the quaternary salt is first converted to 4-18F]fluorobenzaldehyde. Oxidation of the latter provides 4-18F]fluorobenzoic acid, which is converted to 18F]SFB by treatment with N,N-disuccinimidyl carbonate. Using this method, 18F]SFB can be synthesized in decay-corrected radiochemical yields of 30%-35% and a specific radioactivity of 11-12 GBq micromol(-1). The total synthesis and purification time required is about 80 min, starting from delivery of the 18F]fluoride. 18F]SFB remains an optimal reagent for labeling proteins and peptides with 18F because of good conjugation yields and metabolic stability.