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-[F-18] fluorobenzoate ([F-18]SFB), an agent widely used for labeling proteins and peptides with the positron-emitting radionuclide F-18. 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 [F-18] SFB synthesis, the quaternary salt is first converted to 4-[F-18]fluorobenzaldehyde. Oxidation of the latter provides 4-[F-18] fluorobenzoic acid, which is converted to [F-18] SFB by treatment with N,N-disuccinimidyl carbonate. Using this method, [F-18] SFB can be synthesized in decay-corrected radiochemical yields of 30%-35% and a specific radioactivity of 11-12 GBq mu mol(-1). The total synthesis and purification time required is about 80 min, starting from delivery of the [F-18] fluoride. [F-18] SFB remains an optimal reagent for labeling proteins and peptides with F-18 because of good conjugation yields and metabolic stability.