Objective: *Establish a quantitative analysis framework for PI‑2620 tau-PET in progressive supranuclear palsy (PSP);

*Compare tau-PET uptake in PSP versus control subjects;

*Assess correlations with clinical variables and other biomarkers;

*Determine whether baseline uptake predicts longitudinal diagnostic certainty in suggestive PSP.

Background: PSP is a commonly overlooked and diagnosed with remarkable delay, due to unawareness about this atypical parkinsonism with underlying 4R-tauopathy, as well as its overlap with PD, among several other conditions. The current MDS PSP diagnostic criteria include a “suggestive of PSP” category as a proxy of early disease to allow for timely intervention, but it has insufficient specificity in the absence of established, reliable biomarkers. One candidate biomarker to increase PSP diagnostic likelihood in these cases is tau imaging with second generation tracers such as PI2620.

Method: -Participants: This clinical trial with ethics approval has a recruitment target of 30 patients with probable/possible PSP, 20 with suggestive of PSP, and 16 controls (8 without neurological disease and 8 with Parkinson’s disease [PD]). We present preliminary analyses of the first 10 participants from the Barcelona PSP Registry, all meeting current PSP diagnostic criteria, all with brain MRI ruling out exclusion criteria, and all with negative CSF α‑synuclein SAA/T‑QuIC. All participants signed written informed consent.

-Procedure: Dynamic acquisition for 60 minutes following intravenous injection of 18F‑PI‑2620 using a Siemens Biograph Vision X PET scanner. Distribution volume ratios (DVR) for multiple brain regions were computed using cerebellar grey matter as the reference region, analyzed with PMOD software.

-Statistics: ANOVA with Tukey HSD post‑hoc tests.

Results: Dynamic DVR analysis showed significantly increased tracer uptake bilaterally in both the globus pallidus and putamen compared not only with the reference region (cerebellum), but also to cortical areas (frontal, temporal, parietal, occipital).

Conclusion: These preliminary results confirm increased PI‑2620 uptake in anatomically congruent regions in PSP. Recruitment of the remaining PSP, control, and PD participants is under way.

[Funding: CIBER‑BBN + private benefactor / Previous presentation at: NeuroRARE meeting, 26 March 2026, El Escorial, Spain / Our site is part of the CurePSP Centers of Care network]

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MDS Abstracts - https://www.mdsabstracts.org/abstract/quanti-tau-pet-study-of-pi-2620-tau-pet-quantification-in-progressive-supranuclear-palsy/