Exploration of the impact of stereochemistry on the identification of the novel translocator protein PET imaging agent [18F]GE-180

Developing racemic radiotracers, as for racemic therapeutics, is a considerable challenge due to differences of the enantiomers in pharmacokinetics, efficacy and potential toxicity. We have shown that the enantiomers of the promising racemic PET ligand [18F]GE-180 do not share identical performance, with S-[18F]GE-180 demonstrating higher TSPO affinity, higher brain uptake and better retention to the high TSPO-expressing lungs. Furthermore, S-[18F]GE-180 has also been shown to be enantiomerically stable in vivo, with no observed conversation of the eutomer to the distomer. As a single enantiomer, S-[18F]GE-180 retains the beneficial characteristics of the racemate and is a promising imaging agent for imaging neuroinflammation in vivo.