Fully automated F-fluorination of N-succinimidyl-4-[F]fluorobenzoate ([F]SFB) for indirect labelling of nanobodies.

N-succinimidyl-4-[F]fluorobenzoate ([F]SFB), a widely used labeling agent to introduce the 4-[F]fluorobenzoyl-prosthetic group, is normally obtained in three consecutive steps from [F]fluoride ion. Here, we describe an efficient one-step labeling procedure of [F]SFB starting from a tin precursor. This method circumvents volatile radioactive side-products and simplifies automatization. [F]SFB was obtained after HPLC purification in a yield of 42 + 4% and a radiochemical purity (RCP) > 99% (n = 6). In addition, we investigate the automation of the coupling of [F]SFB to a nanobody (cAbBcII10, targeting β-lactamase enzyme) and purification by size exclusion chromatography (PD-10 desalting column) to remove unconjugated reagent. Production and use of [F]SFB were implemented on a radiosynthesis unit (Neptis). The fully automated radiosynthesis process including purification and formulation required 160 min of synthesis time. [F]SFB-labeled nanobody was obtained in a yield of 21 + 2% (activity yield 12 + 1% non-decay corrected) and a radiochemical purity (RCP) of > 95% (n = 3). This approach simplifies [F]SFB synthesis to one-step, enhances the yield in comparison to the previous report and enables the production of radiolabeled nanobody on the same synthesis module.