"In-loop" F-fluorination: A proof-of-concept study.

There is a great demand to develop more cost efficient and robust manufacturing processes for fluorine-18 ( F) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination "in-loop", where [ F]triflyl fluoride was used as the labelling agent. Initial development of the "in-loop" [ F]fluorination method was optimized by reacting [ F]triflyl fluoride with 1,4-dinitrobenzene to form [ F]1-fluoro-4-nitrobenzene. This methodology was then applied for the syntheses of two well-known radiopharmaceuticals, namely, [ F]T807 for imaging of tau protein, and [ F]FEPPA for imaging the translocator protein 18 KDa. Both radiotracers were synthesized and formulated using an automated radiosynthesis module with non-decay corrected radiochemical yields of 27% and 29% (relative [ F]F ), respectively. The overall syntheses times for [ F]T807 and [ F]FEPPA were 65 min and 55 min, 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 >99% and the molar activities were >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.