Home > Publications Database > Developing a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies > print

001     283140
005     20260115103834.0
024 7 _ |a 10.1002/alz70856_104777
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024 7 _ |a 1552-5260
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024 7 _ |a 1552-5279
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037 _ _ |a DZNE-2026-00036
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Frontzkowski, Lukas
|b 0
111 2 _ |a Alzheimer’s Association International Conference
|g AAIC 25
|c Toronto
|d 2025-07-27 - 2025-07-31
|w Canada
245 _ _ |a Developing a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies
260 _ _ |c 2025
336 7 _ |a Abstract
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336 7 _ |a Conference Paper
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Positron-Emission Tomography
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: diagnostic imaging
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Biomarkers: metabolism
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Brain: diagnostic imaging
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Tauopathies: diagnostic imaging
|2 MeSH
650 _ 2 |a Tauopathies: metabolism
|2 MeSH
650 _ 2 |a Neuroimaging
|2 MeSH
700 1 _ |a Gross, Mattes
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700 1 _ |a Roemer-Cassiano, Sebastian
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700 1 _ |a Palleis, Carla
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700 1 _ |a Dehsarvi, Amir
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700 1 _ |a Katzdobler, Sabrina
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700 1 _ |a Dewenter, Anna
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700 1 _ |a Steward, Anna
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700 1 _ |a Biel, Davina
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700 1 _ |a Hirsch, Fabian
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700 1 _ |a Gnoerich, Johannes
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700 1 _ |a Levin, Johannes
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700 1 _ |a Stephens, Andrew W.
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700 1 _ |a Mueller, Andre
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700 1 _ |a Koglin, Norman
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700 1 _ |a Bischof, Gérard N
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700 1 _ |a Kovacs, Gabor G.
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700 1 _ |a Höglinger, Günter U
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700 1 _ |a Brendel, Matthias
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700 1 _ |a Franzmeier, Nicolai
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773 _ _ |a 10.1002/alz70856_104777
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