"In-loop" 18F-fluorination: A proof-of-concept study

There is a great demand to develop more cost-efficient and robust manufacturing processes for fluorine-18 (F-18) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination "in-loop," where [F-18]triflyl fluoride was used as the labelling agent. Initial development of the "in-loop" [F-18]fluorination method was optimized by reacting [F-18]triflyl fluoride with 1,4-dinitrobenzene to form [F-18]1-fluoro-4-nitrobenzene. This methodology was then applied for the syntheses of two well-known radiopharmaceuticals, namely, [F-18]T807 for imaging of tau protein and [F-18]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 [F-18]F-), respectively. The overall syntheses times for [F-18]T807 and [F-18]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/mu mol 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.