PET imaging of tau protein targets: a methodology perspective

Abstract

The two neuropathological hallmarks of Alzheimer's disease (AD) are amyloid-[Formula: see text] plaques and neurofibrillary tangles of tau protein. Fifteen years ago, Positron Emission Tomography (PET) with Pittsburgh Compound B (¹¹C-PiB) enabled selective in-vivo visualization of amyloid-[Formula: see text] plaque deposits and has since provided valuable information about the role of amyloid-[Formula: see text] deposition in AD. The progression of tau deposition has been shown to be highly associated with neuronal loss, neurodegeneration, and cognitive decline. Until recently it was not possible to visualize tau deposition in-vivo, but several tau PET tracers are now available in different stages of clinical development. To date, no tau tracer has been approved by the Food and Drug Administration for use in the evaluation of AD or other tauopathies, despite very active research efforts. In this paper we review the recent developments in tau PET imaging with a focus on in-vivo findings in AD and discuss the challenges associated with tau tracer development, the status of development and validation of different tau tracers, and the clinical information these provide.

Keywords: Aging; Alzheimer’s disease; PET; Radiotracers; Tau Imaging.

Fig. 1

Typical patterns of uptake observed with ¹⁸F-AV-1451 and ¹⁸F-THK5351. 1) (Adapted from Johnson et al. 2016) Coronal PET images of ¹⁸F-AV-1451 80–100 min standardized-uptake-value-ratios (SUVR, with cerebellar reference) from 3 clinically normal (A-C), 2 mild cognitive impairment (D,E) and 2 mild Alzheimer dementia (F,G) participants. Cognitively impaired participants show elevated levels of cortical binding successively involving temporal, parietal, frontal, and occipital cortices. 2) (Adapted from Lockhart et al. 2016) Representative ¹⁸F-THK5351 SUVR 40–60 min PET images of 4 participants (2 controls and 2 AD). These cases present different levels of binding that illustrate the dynamic range of SUVR across participants.

Fig. 2

Patterns of uptake observed with ¹⁸F-MK6240 in a healthy volunteer (HV) and three subjects with AD at different disease stages. ¹⁸F-MK6240 uptake levels and extent increase with disease severity. Courtesy of Cristian Salinas, Biogen.