Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development

Our review shows that multiple new tracers have been developed for proteinopathy targets, particularly tau, as well as the purinoceptor P2X7, phosphodiesterase enzyme PDE10A, and synaptic vesicle glycoprotein 2A (SV2A), amongst others. Some of the most promising of these include ¹⁸F-MK-6240 for tau imaging, ¹¹C-UCB-J for imaging SV2A, ¹¹C-CURB and ¹¹C-MK-3168 for characterisation of fatty acid amide hydrolase, ¹⁸F-FIMX for metabotropic glutamate receptor 1, and ¹⁸F-MNI-444 for imaging adenosine 2A. Our review also identifies recurrent issues within the field. Many of the tracers discussed lack in vivo blocking data, reducing confidence in selectivity. Additionally, late-stage identification of substantial off-target sites for multiple tracers highlights incomplete pre-clinical characterisation prior to translation, as well as human disease state studies carried out without confirmation of test-retest reproducibility.