New PET radiopharmaceuticals for imaging CNS diseases

Positron emission tomography (PET) radiopharmaceuticals for central nervous system (CNS) diseases must fulfil prerequisites and pass clinical evaluations before they enter widespread use in humans. This article aims to give an overview on CNS PET ligands that after pre-clinical development have been applied in humans in recent years. The selected tracers have shown to provide reliable in vivo quantification of the respective molecular target and have been evaluated in at least one group of patients. The first target is the synaptic vesicle protein 2 A (SV2A), a marker for in vivo measurement of synaptic density, which can provide novel insights in the pathology of CNS disorders. Changes of synaptic density have been shown in several neurologic disorders and psychiatric conditions using the SV2A radioligand [ 11 C]UCB-J. The second group of radioligands include second-generation tracers for imaging tau aggregates (e.g., [ 18 F]MK-6240 and [ 18 F]PI-2620). These tau tracers display lower off-target binding and improved imaging properties allowing simplified acquisition protocols. PET radioligands for SV2A and tau aggregates are potential imaging markers for clinical trials and can also become part of routine patient care in the future. Furthermore, radioligands targeting phosphodiesterase 10A (e.g., [ 18 F]MNI-659) have shown to provide reliable assessment of striatal pathology in Huntington's disease gene expansion carries, already at pre-manifest stages. Beyond these, new radioligands for the evaluation of mitochondrial activity ([ 18 F]BCPP-EF), activated astroglia ([ 11 C]BU99008), and the purinoceptor P2X 7 R as marker of neuroinflammation (e.g., [ 11 C]JNJ-717) have emerged. First evaluations of patients with neurodegenerative diseases yielded encouraging results, though non-invasive and simplified quantification methods might not be feasible or need confirmation in larger samples and more patient groups.