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000280249 0247_ $$2ISSN$$a1619-7089
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000280249 037__ $$aDZNE-2025-00927
000280249 041__ $$aEnglish
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000280249 1001_ $$aKling, Agnes$$b0
000280249 245__ $$aExploring the origins of frequent tau-PET signal in vermal and adjacent regions.
000280249 260__ $$aHeidelberg [u.a.]$$bSpringer-Verl.$$c2025
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000280249 520__ $$aOff-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.
000280249 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000280249 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x1
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000280249 650_7 $$2Other$$aCerebellum
000280249 650_7 $$2Other$$aMelanocytes
000280249 650_7 $$2Other$$aMeninges
000280249 650_7 $$2Other$$aOff-target binding
000280249 650_7 $$2Other$$aTau-PET
000280249 650_7 $$2Other$$aVermis
000280249 650_7 $$2NLM Chemicals$$atau Proteins
000280249 650_7 $$2NLM Chemicals$$a((18)F)PI-2620
000280249 650_7 $$2NLM Chemicals$$aFluorine Radioisotopes
000280249 650_7 $$2NLM Chemicals$$aPyridines
000280249 650_2 $$2MeSH$$aNeuroimaging: methods
000280249 650_2 $$2MeSH$$atau Proteins: analysis
000280249 650_2 $$2MeSH$$atau Proteins: metabolism
000280249 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000280249 650_2 $$2MeSH$$aFluorine Radioisotopes: administration & dosage
000280249 650_2 $$2MeSH$$aFluorine Radioisotopes: pharmacology
000280249 650_2 $$2MeSH$$aCerebellar Vermis: diagnostic imaging
000280249 650_2 $$2MeSH$$aCerebellar Vermis: metabolism
000280249 650_2 $$2MeSH$$aCerebellar Vermis: pathology
000280249 650_2 $$2MeSH$$aTauopathies: diagnostic imaging
000280249 650_2 $$2MeSH$$aTauopathies: metabolism
000280249 650_2 $$2MeSH$$aTauopathies: pathology
000280249 650_2 $$2MeSH$$aHumans
000280249 650_2 $$2MeSH$$aMale
000280249 650_2 $$2MeSH$$aFemale
000280249 650_2 $$2MeSH$$aMiddle Aged
000280249 650_2 $$2MeSH$$aAged
000280249 650_2 $$2MeSH$$aAged, 80 and over
000280249 650_2 $$2MeSH$$aCase-Control Studies
000280249 650_2 $$2MeSH$$aPyridines
000280249 7001_ $$aKusche-Palenga, Julia$$b1
000280249 7001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b2$$udzne
000280249 7001_ $$0P:(DE-2719)9002626$$aJäck, Alexander$$b3$$udzne
000280249 7001_ $$0P:(DE-2719)9002620$$aBernhardt, Alexander M$$b4$$udzne
000280249 7001_ $$aFrontzkowski, Lukas$$b5
000280249 7001_ $$0P:(DE-2719)9003667$$aRömer, Sebastian$$b6$$udzne
000280249 7001_ $$aSlemann, Luna$$b7
000280249 7001_ $$aZaganjori, Mirlind$$b8
000280249 7001_ $$aScheifele, Maximilian$$b9
000280249 7001_ $$0P:(DE-2719)9002242$$aPaeger, Lars$$b10$$udzne
000280249 7001_ $$0P:(DE-2719)9002485$$aBischof, Gérard N$$b11
000280249 7001_ $$0P:(DE-2719)2812285$$avan Eimeren, Thilo$$b12$$udzne
000280249 7001_ $$0P:(DE-2719)2811239$$aDrzezga, Alexander$$b13$$udzne
000280249 7001_ $$0P:(DE-2719)2814810$$aSabri, Osama$$b14$$udzne
000280249 7001_ $$aRullmann, Michael$$b15
000280249 7001_ $$aBarthel, Henryk$$b16
000280249 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b17$$udzne
000280249 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b18$$udzne
000280249 7001_ $$aFranzmeier, Nicolai$$b19
000280249 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter$$b20$$udzne
000280249 7001_ $$aRoeber, Sigrun$$b21
000280249 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b22$$udzne
000280249 7001_ $$0P:(DE-2719)9001652$$aGnoerich, Johannes$$b23$$eLast author$$udzne
000280249 773__ $$0PERI:(DE-600)2098375-X$$a10.1007/s00259-025-07199-x$$gVol. 52, no. 10, p. 3519 - 3533$$n10$$p3519 - 3533$$tEuropean journal of nuclear medicine and molecular imaging$$v52$$x1619-7070$$y2025
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