Increased basal ganglia binding of ¹⁸F‐AV‐1451 in patients with progressive supranuclear palsy

Abstract

BackgroundProgressive supranuclear palsy (PSP) is difficult to diagnose accurately. The recently developed tau PET tracers may improve the diagnostic work‐up of PSP.MethodsRegional tau accumulation was studied using 18F‐AV‐1451 PET in 11 patients with PSP and 11 age‐matched healthy controls in the Swedish BioFinder study.Results 18F‐AV‐1451 standard uptake volume ratios were significantly higher in the basal ganglia in PSP patients when compared with controls (globus pallidus 1.75 vs 1.50; putamen 1.51 vs 1.35). Retention in the basal ganglia was correlated with age in both groups (r = .43–.78, P < .05). In PSP, we observed a significant correlation between clinical deterioration measured with the PSP rating scale and standard uptake volume ratios in the globus pallidus (r = .74, P < .05). However, no 18F‐AV‐1451 retention was observed in the cerebral cortex or white matter of either PSP patients or controls, and autoradiography did not reveal any specific binding of AV‐1451 to PSP tau aggregates.ConclusionWe found higher 18F‐AV‐1451 retention in the basal ganglia of PSP patients when compared with healthy elderly controls, but also increases with age in both controls and patients. As a result of the overlap in retention between diagnostic groups and the age‐dependent increase present also in controls, 18F‐AV‐1451 PET might not reliably distinguish individual patients with PSP from controls. However, further studies are needed to evaluate whether 18F‐AV‐1451 PET might be useful as a progression marker in clinical PSP trials. © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

18F‐flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study

“…This pattern, often referred to as “off-target” binding, partially overlapped with the distribution and degree of binding seen in patients with PSP, as reported previously. 11,17,19 18 F-flortaucipir scans of PD patients resembled control scans.…”

“…7 While previous studies have reported preliminary 18 F-flortaucipir findings in relatively small numbers of PSP patients studied at single sites, our study found that 18 F-flortaucipir PET provided robust group-level differences and strong single-subject discrimination between PSP and both normal and disease (PD) controls when combining data across multiple sites and PET scanner models. 11–15 The most consistent finding when comparing PSP patients to controls across studies has been bilaterally elevated 18 F-flortaucipir uptake in the globus pallidus. Elevated uptake in subthalamic nucleus and dorsal midbrain is also a consistent feature, along with the relative absence of tracer retention in pons, cortex and subcortical WM, while uptake in dentate nucleus has been variable.…”

“…Elevated uptake in subthalamic nucleus and dorsal midbrain is also a consistent feature, along with the relative absence of tracer retention in pons, cortex and subcortical WM, while uptake in dentate nucleus has been variable. Associations of 18 F-flortaucipir signal with composite measures of disease severity have been inconsistent, 11–13,15 which may be explained by disease heterogeneity in both topographic patterns of binding and clinical progression. Indeed, we identified potential differences in binding patterns between distinct clinical variants of PSP (PSP-PAGF and PSP-CBS compared to PSP-RS) corresponding to reported differences in the distribution of tau pathology across these variants at autopsy, 3 though these findings need to be replicated in larger samples.…”

“…8 One tracer, the pyrido-indole derivative 18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807), has shown early promise as a marker of tau pathology in AD, 9,10 and several in vivo studies of 18 F-flortaucipir in smaller samples of PSP patients studied at individual centers reported increased uptake in regions expected to harbor tau pathology. 11–15 However, discrepancies have been noted between these positive in vivo results and in vitro autoradiography studies that showed high affinity binding of 18 F-flortaucipir to PHF tau but low affinity or no targeted binding to straight filamentous tau in PSP and CBD. 16–20 …”

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

“…As aforementioned, tau pathology in AD and FTLD-Tau have different biochemical and conformational properties which could contribute. Some studies have shown the ability to discriminate PSPS patients from controls and from patients with AD [26, 75, 76]; however, evidence for potential off-target binding in melanin-containing cells has been described in regions susceptible to PSP tauopathy [74] (i.e., substantia nigra, basal ganglia) which could influence interpretation. Emerging autopsy studies provide good correlation with topography of FTLD-Tau pathology post-mortem and antemortem [ 18 F]AV1451 signal [26, 77], suggesting potential utility in FTLD-Tau but further study with tissue validation for this and other tracers is needed.…”