Imaging pathological tau in atypical parkinsonisms: A review

Anastassia M Mena; Antonio P Strafella

doi:10.1016/j.prdoa.2022.100155

Imaging pathological tau in atypical parkinsonisms: A review

Clin Park Relat Disord. 2022 Jul 16:7:100155. doi: 10.1016/j.prdoa.2022.100155. eCollection 2022.

Authors

Anastassia M Mena^{1

2}, Antonio P Strafella^{1

3

2

4}

Affiliations

¹ Brain Health Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
² Institute of Medical Science, University of Toronto, Ontario, Canada.
³ Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Brain Institute, UHN, University of Toronto, Ontario, Canada.
⁴ Edmond J. Safra Parkinson Disease Program & Morton and Gloria Shulman Movement Disorder Unit, Neurology Division, Dept. of Medicine, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada.

Abstract

Atypical parkinsonisms (APs) are a group of diseases linked to tau pathology. These include progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In the initial stages, these APs may have similar clinical manifestations to Parkinson's disease (PD) and other parkinsonisms: bradykinesia, postural instability, tremor, and cognitive decline. Because of this, one major hurdle is the accurate early diagnosis of APs. Recent advances in positron emission tomography (PET) radiotracer development have allowed for targeting pathological tau in Alzheimer's disease (AD). Currently, work is still in progress for identifying a first-in-class radiotracer for imaging tau in APs. In this review, we evaluate the literature on in vitro and in vivo testing of current tau PET radiotracers in APs. The tau PET tracers assessed include both first-generation tracers ([18F]AV-1451, [18F]FDDNP, [18F]THK derivatives, and [11C]PBB3) and second-generation tracers ([18F]PM-PBB3, [18F]PI-2620, [18F]RO-948, [18F]JNJ-067, [18F]MK-6240, and [18F]CBD-2115). Concerns regarding off-target binding to cerebral white matter and the basal ganglia are still prominent with first-generation tracers, but this seems to have been mediated in a handful of second-generation tracers, including [18F]PI-2620 and [18F]PM-PBB3. Additionally, these two tracers and [18F]MK-6240 show promising results for imaging PSP- and CBD-tau. Overall, [18F]AV-1451 is the most widely studied tracer but the mixed results regarding its efficacy for use in imaging AP-tau is a cause for concern moving forward. Instead, future work may benefit from focusing on the second-generation radiotracers which seem to have a higher specificity for AP-tau than those originally developed for imaging AD-tau.

Keywords: CBD; CBD, corticobasal degeneration; Neuroimaging; PET; PET, positron emission tomography; PSP; PSP, progressive supranuclear palsy; Parkinsonism; Parkinson’s disease; SPECT; SPECT, single-photon emission computerized tomography.

Publication types

Review