¹⁸F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear Palsy

Abstract

Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder which can be imaged by the tau positron emission tomography (PET) tracer ¹⁸F-PI-2620. The in vivo diagnosis is currently established on clinical grounds and supported by midbrain atrophy estimation in structural magnetic resonance imaging (MRI). Here, we investigate whether ¹⁸F-PI-2620 tau PET has the potential to improve the imaging diagnosis of PSP. Methods: In this multi-center observational study, dynamic (0-60min p.i.) ¹⁸F-PI-2620 PET and structural MRI data of 36 patients with PSP, 22 with PSP-Richardson’s syndrome (PSP-RS) and 14 with clinical phenotypes other than RS, i.e. variant PSP (vPSP), and those of 10 age-matched healthy controls (HCs) were analyzed. The PET data underwent kinetic modeling which resulted in distribution volume ratio (DVR) images. These and the MRI images were visually assessed by three blinded experts each for typical PSP signs. Furthermore, established midbrain atrophy parameters were measured in structural MRI, and regional DVRs in typical tau-in-PSP target regions in the PET data. Results: Visual assessments discriminated PSP patients and HCs with an accuracy of 63% for MRI, and 80% for the combination of MRI and ¹⁸F-PI-2620 PET. As compared to patients of the PSP-RS subgroup, those of the vPSP subgroup profited more in terms of sensitivity from the addition of the visual ¹⁸F-PI-2620 PET to the visual MRI information (35% vs. 22%). In quantitative image evaluation, midbrain /pons area ratio and globus pallidus DVRs discriminated best between the PSP patients and HCs, with sensitivities/specificities of 83/90% for MRI, and 94/100% for the combination of MRI and ¹⁸F-PI-2620 PET. The gain of sensitivity by adding ¹⁸F-PI-2620 PET to MRI data was more marked in clinically less-affected as compared to more-affected patients (37% vs. 19% for visual, and 16% vs. 12% for quantitative image evaluation). Conclusion: These results provide evidence for an improved imaging-based PSP diagnosis by adding ¹⁸F-PI-2620 tau PET to structural MRI. This approach seems to be particularly promising at earlier disease stages and could be of value both for improving early clinical PSP diagnosis and for enriching PSP cohorts for trials of disease-modifying drugs.