Objective: To evaluate change in AV-1451 positron emission tomography (PET) imaging in patients with Progressive Supranuclear Palsy (PSP) and Cortico-Basal Syndrome (CBS) over 9 months follow-up.

Background: Biomarkers for PSP and CBS have the potential to improve early diagnosis and accelerate therapeutic development. We previously reported modest differences in 18F-AV-1451 PET uptake between patients with PSP and CBS and healthy controls.  However, the usefulness of AV-1451 as a marker of disease progression in non-AD tauopathies has not been extensively evaluated.

Methods: Participants with PSP or CBS were recruited at 5 clinical sites.  Only subjects with negative amyloid PET scans were included.  Participants underwent PET imaging 75-105 minutes after injection of 10 mCi (370 mBq) F18-AV-1451.  Images were co-registered with MRI and standardized uptake value ratios (SUVr) were derived in four regions of interest: bilateral dentate nuclei of the cerebellum and bilateral globus pallidus relative to a cerebellar reference region. A combined SUVr was calculated as the average of the SUVr for these 4 regions.  Participants also had clinical evaluations including the PSP rating scale (PSP-RS). Changes from baseline to 9 months follow-up were calculated for the regional and composite SUVr and for clinical assessments.

Results: 18 participants with PSP and 5 participants with CBS were enrolled.  At baseline, the mean PSP-RS score for PSP and CBD cases combined was 31.4 (range 13 to 45).  For the combined PSP/CBS group, there was no significant change in the combination SUVr from baseline to 9 months (mean baseline SUVr = 1.35 vs. mean follow-up SUVr = 1.36; p = 0.19).  There was also no significant change for the combination region when only PSP subjects were included (mean baseline SUVr = 1.36 vs. mean follow-up SUVr = 1.37; p = 0.42).  Over 9 months, there was significant clinical decline on the PSP-RS for the combined PSP/CBD group with a mean score of 31 at baseline and 41 at follow-up (p<0.0001), with similar results when the analysis was confined to only PSP subjects. 

Conclusions: In this pilot study of patients with mild-to-moderate PSP and CBS, there was no change in mean F18-AV-1451 in spite of significant change in clinical severity.  The results of this study do not support F18-AV-1451 PET as a marker of disease progression in early-to-moderate PSP/CBS patients over a 9 month period of follow up.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-av-1451-pet-imaging-in-progressive-supranuclear-palsy-and-cortico-basal-syndrome/