Tau Positron Emission Tomography (PET) Imaging: Past, Present, and Future

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia among the elderly population. The good correlation of the density and neocortical spread of neurofibrillary tangles (NFTs) with clinical AD disease progression offers an opportunity for the early diagnosis and staging using a noninvasive imaging technique such as positron emission tomography (PET). Thus, PET imaging of NFTs not only holds promise as a diagnostic tool but also may enable the development of disease modifying therapeutics for AD. In this review, we focus on the structural diversity of tau PET tracers, the challenges related to the identification of high affinity and highly selective NFT ligands, and recent progress in the clinical development of tau PET radioligands.

18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

“…PET imaging of tau is expected to provide spatiotemporal information on the progression of tau pathology in the living brain. Therefore, this technique will facilitate accurate tauopathy diagnosis, precise assessment of disease severity and therapeutic efficacy, and patient enrolment for antitau therapeutic trials (8)(9)(10).…”

Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles

“…1) (5,6). 18 F-AV-1451 ( 18 F-T807) was the first PET tracer to show promise for quantifying NFT pathology in AD patients (7) and is currently the most widely studied NFT PET tracer.…”

Fully automated synthesis of [18F]T807, a PET tau tracer for Alzheimer’s disease

“…indole (2): A solution of compound 1 (0.84 g, 3.0 mmol) in 30 mL of triethyl phosphate was heated at 110 °C for 3 h under N 2 . The reaction was monitored with TLC for every 1 h. After the starting material was disappeared, the reaction mixture was cooled down, and volatiles were removed in vacuo.…”

“…[1][2][3] The exact causes of AD are not fully understood. 4 Currently there is no prevention or cure, and clinical drug trials have greater than 90% failure rate.…”

“…The halogen-tin exchange reaction of 5-bromo-2-nitropyridine with hexamethylditin in refluxing dioxane in the presence of the catalyst Pd(PPh 3 ) 4 gave 4 in 55% yield. Another precursor t-Boc-protected T807P was prepared from T807P with di-tert-butyl-dicarbonate {(Boc) 2 O} using base catalyst…”