% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kling:280249,
      author       = {Kling, Agnes and Kusche-Palenga, Julia and Palleis, Carla
                      and Jäck, Alexander and Bernhardt, Alexander M and
                      Frontzkowski, Lukas and Römer, Sebastian and Slemann, Luna
                      and Zaganjori, Mirlind and Scheifele, Maximilian and Paeger,
                      Lars and Bischof, Gérard N and van Eimeren, Thilo and
                      Drzezga, Alexander and Sabri, Osama and Rullmann, Michael
                      and Barthel, Henryk and Levin, Johannes and Herms, Jochen
                      and Franzmeier, Nicolai and Höglinger, Günter and Roeber,
                      Sigrun and Brendel, Matthias and Gnoerich, Johannes},
      title        = {{E}xploring the origins of frequent tau-{PET} signal in
                      vermal and adjacent regions.},
      journal      = {European journal of nuclear medicine and molecular imaging},
      volume       = {52},
      number       = {10},
      issn         = {1619-7070},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer-Verl.},
      reportid     = {DZNE-2025-00927},
      pages        = {3519 - 3533},
      year         = {2025},
      abstract     = {Off-target binding remains a significant challenge in
                      tau-PET neuroimaging. While off-targets including monoamine
                      oxidase enzymes and neuromelanin-containing cells have been
                      identified, recent studies indicated a relevant binding of
                      novel tau tracers to melanin-containing structures. To date,
                      little is known about the effect of melanocytes in the
                      meninges on tracer signals in brain PET data. Thus, we aimed
                      to identify the target structure causal for the frequently
                      observed [18F]PI-2620 PET signal in the vermis and adjacent
                      cerebellar regions.274 participants underwent dynamic
                      [18F]PI-2620 tau-PET: 3/4R-tauopathies (n = 85),
                      4R-tauopathies (n = 147), tau-negative disease controls (n =
                      24), and healthy controls (n = 18). Standardized uptake
                      value ratio (SUVR) and kinetic parameters including the
                      distribution volume ratio (DVR), tracer clearance (k2) and
                      relative perfusion (R1), were compared among the cohorts and
                      sexes using the Automated Anatomical Labelling (AAL) atlas.
                      Age and p-Tau levels in cerebrospinal fluid (CSF) were
                      assessed for their relationship with vermal tau-PET signal.
                      Furthermore, we combined autoradiographic and histochemical
                      experiments on post-mortem brain tissue of deceased patients
                      (n = 9).Male participants revealed higher mean vermal
                      [18F]PI-2620 DVR (0.95 ± 0.13; vs. females 0.88 ± 0.10, p
                      < 0.0001). Sex-related differences were most pronounced in
                      the 3/4R-tauopathy cohort (p < 0.0001). Mean SUVRVer/Cbl, k2
                      and correlation analyses of kinetic parameters did not
                      differ among groups. Histological assessments revealed
                      co-localization of leptomeningeal pigmented cells with
                      strong autoradiography signal spots within the vermal
                      fissures. Tau-related autoradiography signals, age or p-Tau
                      levels did not correlate significantly with tau-PET signals.
                      Iron deposits did not cause relevant autoradiography signals
                      in the vermis.Leptomeningeal melanocytes are the primary
                      target structure for [18F]PI-2620 PET binding in anterior
                      vermis, whereas iron and tau deposits do not contribute
                      significantly.},
      keywords     = {Neuroimaging: methods / tau Proteins: analysis / tau
                      Proteins: metabolism / Positron-Emission Tomography: methods
                      / Fluorine Radioisotopes: administration $\&$ dosage /
                      Fluorine Radioisotopes: pharmacology / Cerebellar Vermis:
                      diagnostic imaging / Cerebellar Vermis: metabolism /
                      Cerebellar Vermis: pathology / Tauopathies: diagnostic
                      imaging / Tauopathies: metabolism / Tauopathies: pathology /
                      Humans / Male / Female / Middle Aged / Aged / Aged, 80 and
                      over / Case-Control Studies / Pyridines / Cerebellum (Other)
                      / Melanocytes (Other) / Meninges (Other) / Off-target
                      binding (Other) / Tau-PET (Other) / Vermis (Other) / tau
                      Proteins (NLM Chemicals) / ((18)F)PI-2620 (NLM Chemicals) /
                      Fluorine Radioisotopes (NLM Chemicals) / Pyridines (NLM
                      Chemicals)},
      cin          = {AG Haass / Clinical Research (Munich) / AG Herms / AG
                      Boecker / AG Levin},
      ddc          = {610},
      cid          = {I:(DE-2719)1110007 / I:(DE-2719)1111015 /
                      I:(DE-2719)1110001 / I:(DE-2719)1011202 /
                      I:(DE-2719)1111016},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40100387},
      pmc          = {pmc:PMC12316827},
      doi          = {10.1007/s00259-025-07199-x},
      url          = {https://pub.dzne.de/record/280249},
}