TY  - CONF
AU  - Frontzkowski, Lukas
AU  - Gross, Mattes
AU  - Roemer-Cassiano, Sebastian
AU  - Palleis, Carla
AU  - Dehsarvi, Amir
AU  - Katzdobler, Sabrina
AU  - Dewenter, Anna
AU  - Steward, Anna
AU  - Biel, Davina
AU  - Hirsch, Fabian
AU  - Gnoerich, Johannes
AU  - Levin, Johannes
AU  - Stephens, Andrew W.
AU  - Mueller, Andre
AU  - Koglin, Norman
AU  - Bischof, Gérard N
AU  - Kovacs, Gabor G.
AU  - Höglinger, Günter U
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - Developing a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies
JO  - Alzheimer's and dementia
VL  - 21
IS  - S2
SN  - 1552-5260
M1  - DZNE-2026-00036
SP  - e104777
PY  - 2025
AB  - 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.
T2  - Alzheimer’s Association International Conference
CY  - 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2  - 27 Jul 2025 - 31 Jul 2025
M2  - Toronto, Canada
KW  - Humans
KW  - Positron-Emission Tomography
KW  - Supranuclear Palsy, Progressive: diagnostic imaging
KW  - Supranuclear Palsy, Progressive: metabolism
KW  - Male
KW  - Female
KW  - tau Proteins: metabolism
KW  - Aged
KW  - Biomarkers: metabolism
KW  - Middle Aged
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Tauopathies: diagnostic imaging
KW  - Tauopathies: metabolism
KW  - Neuroimaging
KW  - tau Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
DO  - DOI:10.1002/alz70856_104777
UR  - https://pub.dzne.de/record/283140
ER  -