Overview of tau PET molecular imaging

Abstract

Purpose of review: This article reviews tau PET imaging with an emphasis on first-generation and second-generation tau radiotracers and their application in neurodegenerative disorders, including Alzheimer's disease and non-Alzheimer's disease tauopathies.

Recent findings: Tau is a critical protein, abundant in neurons within the central nervous system, which plays an important role in maintaining microtubules by binding to tubulin in axons. In its abnormal hyperphosphorylated form, accumulation of tau has been linked to a variety of neurodegenerative disorders, collectively referred to as tauopathies, which include Alzheimer's disease and non-Alzheimer's disease tauopathies [e.g., corticobasal degeneration (CBD), argyrophilic grain disease, progressive supranuclear palsy (PSP), and Pick's disease]. A number of first-generation and second-generation tau PET radiotracers have been developed, including the first FDA-approved agent [18F]-flortaucipir, which allow for in-vivo molecular imaging of underlying histopathology antemortem, ultimately guiding disease staging and development of disease-modifying therapeutics.

Summary: Tau PET is an emerging imaging modality in the diagnosis and staging of tauopathies.

FIGURE 1.

Fifty-year-old man with amnestic mild cognitive impairment. Montreal Cognitive Assessment (MoCA) score was 20 of 30. ¹⁸F-flortacupir PET/MRI in the axial, coronal and sagittal plane demonstrates increased tracer uptake with standardized uptake value ratio more than 1.22 relative to cerebellar gray matter in a combined region including the entorhinal cortex, amygdala, inferior temporal gyrus and lateral occipital cortex. This corresponds to in vivo tau-PET Stage I/II, with Z-score in the entorhinal cortex more than 2.5 compared with cognitively normal controls, as defined by Cho et al. [40].

FIGURE 2.

Comparison of ¹⁸F-florbetaben amyloid-PET and [¹⁸F] PI-2620 tau PET obtained in a 56-year-old subject with Mini-Mental State Examination (MMSE) score of 23. Images were normalized to the cerebellar gray matter and co-registered to the subject’s MRI. Please note increased cortical amyloid burden (A+) with associated tau-PET binding in disease relevant-areas (T+), with lack of off-target binding in the choroid plexus and subcortical structures typically seen with first-generation tau radiotracers. Reproduced with permission [27^■■].

FIGURE 3.

Sixty-year-old man presenting with memory loss. Amyloid PET scan with Pittsburgh Compound B demonstrates diffuse cortical amyloid deposition (a). Coronal T1-weighted MRI demonstrates no significant hippocampal or lobar-specific atrophy (b). Axial (c) and coronal (d) tau PET images utilizing the 2nd generation tracer 18F-MK6240 fused to T1-weighted MRI show increased tau deposition in the bilateral mesial temporal lobes.

FIGURE 4.

Average [¹⁸F]-PI-2620 distribution volume ratio binding maps presented as axial overlays on a standard MRI template for patients with progressive supranuclear palsy-Richardson’s syndrome, progressive supranuclear palsy-non-Richardson’s syndrome, α-synucleinopathy, Alzheimer’s disease and healthy controls. Please note disease-specific uptake in the basal ganglia, subthalamic nucleus, substantia nigra and dentate nuclei in progressive supranuclear palsy patients. Reproduced with permission [22^■■].