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

J Labelled Comp Radiopharm. 2019 Jun 15;62(7):292-297. doi: 10.1002/jlcr.3751.


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.

Keywords: PET; fluorine-18; loop; radiochemistry; radiofluorination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cost-Benefit Analysis
  • Fluorine Radioisotopes / chemistry*
  • Halogenation*
  • Humans
  • Isotope Labeling
  • Neuroimaging
  • Positron-Emission Tomography
  • Radiochemistry / economics
  • Radiochemistry / methods*
  • Receptors, GABA / metabolism
  • tau Proteins / metabolism


  • Fluorine Radioisotopes
  • MAPT protein, human
  • Receptors, GABA
  • TSPO protein, human
  • tau Proteins
  • Fluorine-18