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@INPROCEEDINGS{Frontzkowski:283140,
      author       = {Frontzkowski, Lukas and Gross, Mattes and Roemer-Cassiano,
                      Sebastian and Palleis, Carla and Dehsarvi, Amir and
                      Katzdobler, Sabrina and Dewenter, Anna and Steward, Anna and
                      Biel, Davina and Hirsch, Fabian and Gnoerich, Johannes and
                      Levin, Johannes and Stephens, Andrew W. and Mueller, Andre
                      and Koglin, Norman and Bischof, Gérard N and Kovacs, Gabor
                      G. and Höglinger, Günter U and Brendel, Matthias and
                      Franzmeier, Nicolai},
      title        = {{D}eveloping a {N}ovel {R}eference {R}egion for
                      {PI}‐2620‐{PET} {I}maging to {F}acilitate {A}ssessment
                      of 4‐{R}epeat {T}auopathies},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {S2},
      issn         = {1552-5260},
      reportid     = {DZNE-2026-00036},
      pages        = {e104777},
      year         = {2025},
      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.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Positron-Emission Tomography / Supranuclear Palsy,
                      Progressive: diagnostic imaging / Supranuclear Palsy,
                      Progressive: metabolism / Male / Female / tau Proteins:
                      metabolism / Aged / Biomarkers: metabolism / Middle Aged /
                      Brain: diagnostic imaging / Brain: metabolism / Tauopathies:
                      diagnostic imaging / Tauopathies: metabolism / Neuroimaging
                      / tau Proteins (NLM Chemicals) / Biomarkers (NLM Chemicals)},
      cin          = {Clinical Research (Munich) / AG Levin / AG Haass},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1111016 /
                      I:(DE-2719)1110007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      doi          = {10.1002/alz70856_104777},
      url          = {https://pub.dzne.de/record/283140},
}