Several 11C radioligands of the A2R have been developed for PET imaging of this receptor as shown in Figure 4. These most studied ligands are 2 xanthine-derived compounds, [11C]TMSX ([11C]KF18446) and [11C]KF21213, and 2 nonxanthene compounds, [11C]SCH442416 and [11C]Preladenant.25 Within the xanthene-based PETs, [11C]TMSX has been successfully evaluated in vivo in rodent (mice and rat) and in nonhuman primate (monkeys) and has detected A2ARs in the brain with good striatum/cerebellum uptake ratio in the above animal species.25,120-122 Another xanthine PET ligand [11C]KF21213 also displayed good striatal/cerebellum uptake ratio in rodent (10.5 at 60 minutes) but showed a lower signal to noise ratio in nonhuman primate brain.121,123 Among the latter 2 xanthene-derived PET radioligands, [11C]TMSX has been the most suitable radiotracer for mapping the A2ARs and exhibited the highest binding potential in the striatum.120 Currently, [11C]TMSX is the most broadly used PET imaging radioligand for visualization of A2A receptor in the brain and therefore is considered the gold standard for brain imaging of the A2A receptors.121,122 A major consideration when using this tracer is the fact that dosing and blood sampling need to be performed under dimmed light due to [11C]TMSX photoisomerization.
