Continuous-Flow Synthesis of N-Succinimidyl 4-[(18)F]fluorobenzoate Using a Single Microfluidic Chip

In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of (18)F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [(18)F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [(18)F]SFB. In the synthesis of [(18)F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [(18)F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [(18)F]SFB.