Facile synthesis of N-succinimidyl 4-[¹⁸F]fluorobenzoate ([ ¹⁸F]SFB) for protein labeling

An efficient preparation of N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) based on a convenient three-step, one-pot procedure is described. [¹⁸F]Fluorination of the precursor ethyl 4-(trimethylammonium triflate)benzoate gave ethyl 4-[¹⁸F] fluorobenzoate. Saponification of the ethyl 4-[¹⁸F]fluorobenzoate with aqueous tetrapropylammonium hydroxide yielded the corresponding 4-[ ¹⁸F]fluorobenzoate salt ([¹⁸F]FBA), which was then treated with N,N,N,N′-tetramethyl-O-(N-succinimidyl)uronium hexafluorophosphate. The purified [¹⁸F]SFB was used for the labeling of Avastin™ (Bevacizumab) through [¹⁸F]fluorobenzoylation of the Avastin's α-amino groups. The decay-corrected radiochemical yields of [ ¹⁸F]SFB were as high as 44% (based on [¹⁸F]fluoride (n = 10) with a synthesis time of less than 60 min. [¹⁸F]Avastin was produced in decay-corrected radiochemical yields of up to 42% (n = 5) within 30 min (based on [¹⁸F]SFB). The radiochemical purities of [ ¹⁸F]SFB and [¹⁸F]Avastin were greater than 95%.