The importance of tau tracers in the diagnosis of neurodegenerative diseases

The accumulation of tau protein aggregates in different regions of the brain is a distinctive hallmark of tauopathies, a class of important and prevalent neurodegenerative disorders. Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), and certain types of frontotemporal lobar degeneration (FTLD) are the most well-known tauopathies. It is clear that the accurate and early identification of tau aggregates in the living brain is crucial for initiating suitable interventions at the onset of neurodegenerative diseases, monitoring the progress of these diseases, and assessing the effectiveness of novel treatments. Accordingly, during the past several decades, significant efforts have been made to develop tau-specific positron emission tomography (PET) radioligands for detecting tau aggregates in the living brain, which resulted in the development of several prominent tau PET tracers, including first-generation tracers like Tauvid, [ 11 C]-PBB3, [ 18 F]-THK5117, [ 18 F]- THK5351, and [ 18 F]- THK5105, and second-generation tracers like [ 18 F]-RO948, [ 18 F]-JNJ311, [ 18 F]-PI2620, [ 18 F]PM-PBB3, and [ 18 F]-GTP1. Recently, Tauvid has been approved by the FDA as a tau PET tracer for clinical use, while others are undergoing clinical trials or are in the research stage. This review provides an overview of the neuropathological characteristics, clinical uses, and synthesis methods of several reported tau PET tracers.