“In‐loop” 18 F‐fluorination: A proof‐of‐concept study

There is a great demand to develop more cost‐efficient and robust manufacturing processes for fluorine‐18 ( 18 F) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination “in‐loop,” where [ 18 F]triflyl fluoride was used as the labelling agent. Initial development of the “in‐loop” [ 18 F]fluorination method was optimized by reacting [ 18 F]triflyl fluoride with 1,4‐dinitrobenzene to form [ 18 F]1‐fluoro‐4‐nitrobenzene. This methodology was then applied for the syntheses of two well‐known radiopharmaceuticals, namely, [ 18 F]T807 for imaging of tau protein and [ 18 F]FEPPA for imaging the translocator protein 18 KDa. Both radiotracers were synthesized and formulated using an automated radiosynthesis module with nondecay corrected radiochemical yields of 27% and 29% (relative [ 18 F]F − ), respectively. The overall syntheses times for [ 18 F]T807 and [ 18 F]FEPPA were 65 and 55 minutes, respectively. In these cases, our “in‐loop” radiofluorination methodology enabled us to obtain equal or superior yields compared with conventional reactions in a vial. The radiochemical purities were more than 99%, and the molar activities were more than 350 GBq/μmol at the end‐of‐synthesis for both radiotracers. This novel method is simple, efficient, and allows for a reliable production of radiofluorinated compounds and radiopharmaceuticals.