Abstract/Journal Article

DZNE-2026-00036

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Developing a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies

Frontzkowski, L. ; Gross, M. ; Roemer-Cassiano, S. ; Palleis, C.DZNE* ; Dehsarvi, A. ; Katzdobler, S.DZNE* ; Dewenter, A. ; Steward, A. ; Biel, D. ; Hirsch, F. ; Gnoerich, J.Extern* ; Levin, J.DZNE* ; Stephens, A. W. ; Mueller, A. ; Koglin, N. ; Bischof, G. N. ; Kovacs, G. G. ; Höglinger, G. U.DZNE* ; Brendel, M.DZNE* ; Franzmeier, N.

2025

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Please use a persistent id in citations: doi:10.1002/alz70856_104777

Abstract: Neurodegenerative 4-repeat (4R) tauopathies commonly manifest as progressive supranuclear palsy (PSP). PSP patients show elevated PI-2620-PET in subcortical 4R tau predilection sites (e.g., globus pallidus), suggesting PI-2620-PET as a promising 4R tau neuroimaging candidate. However, optimal quantification of PI-2620-PET in 4R tauopathies remains challenging, as conventional cerebellar tau-PET reference regions also accumulate 4R tau. We aimed to use unbiased image-derived input function (IDIF) PET data to determine an optimized PET reference region for in vivo quantification of 4R tau.We obtained 60-minute dynamic PI-2620-PET in 54 PSP Richardson Syndrome (PSP-RS) patients and 19 healthy controls (HC), applying IDIF-modeling using carotid timeseries to assess unbiased PI-2620-PET binding and determine total distribution volume (VT). Through an iterative approach, we intensity-normalized VT-images against white-matter regions in the Hammers brain atlas, identifying regions where intensity-normalized pallidum PET values showed the largest PSP-RS vs. HC differences. White-matter regions with strongest PSP-RS vs. HC differences surviving multiple-comparison correction were summarized into a single reference region spanning bilateral temporo-orbital white-matter. This ROI was then used to determine SUVRs using conventional 20-40 minute PI-2620-PET data in PSP-RS, a PSP-non-RS validation sample (n = 63), as well as non-tau disease controls (i.e., alpha-synucleinopathies, n = 20; Alzheimer's disease, n = 23).Using PI-2620 SUVRs obtained with the temporo-orbital white-matter reference, we detected strong PSP-RS vs. HC group differences in basal ganglia SUVRs using voxel-wise comparisons (p <0.001, FWE-cluster corrected). Similar basal ganglia differences were detected for PSP-non-RS vs. HC, but not for alpha-syn (no group differences) or AD vs. HC (cortical AD-like group differences). In contrast, minimal group differences were found using a conventional inferior cerebellar grey matter reference region.Our findings strongly suggest temporo-orbital white-matter is superior to inferior cerebellum as a reference region for PI-2620-PET imaging in 4R tauopathies, due to increased sensitivity and purported specificity for 4R tau.

Keyword(s): Humans (MeSH) ; Positron-Emission Tomography (MeSH) ; Supranuclear Palsy, Progressive: diagnostic imaging (MeSH) ; Supranuclear Palsy, Progressive: metabolism (MeSH) ; Male (MeSH) ; Female (MeSH) ; tau Proteins: metabolism (MeSH) ; Aged (MeSH) ; Biomarkers: metabolism (MeSH) ; Middle Aged (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Tauopathies: diagnostic imaging (MeSH) ; Tauopathies: metabolism (MeSH) ; Neuroimaging (MeSH) ; tau Proteins ; Biomarkers

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Clinical Neurodegeneration (AG Levin)
3. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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