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000283140 041__ $$aEnglish
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000283140 1001_ $$aFrontzkowski, Lukas$$b0
000283140 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283140 245__ $$aDeveloping a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies
000283140 260__ $$c2025
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000283140 520__ $$aNeurodegenerative 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.
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000283140 650_7 $$2NLM Chemicals$$atau Proteins
000283140 650_7 $$2NLM Chemicals$$aBiomarkers
000283140 650_2 $$2MeSH$$aHumans
000283140 650_2 $$2MeSH$$aPositron-Emission Tomography
000283140 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: diagnostic imaging
000283140 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: metabolism
000283140 650_2 $$2MeSH$$aMale
000283140 650_2 $$2MeSH$$aFemale
000283140 650_2 $$2MeSH$$atau Proteins: metabolism
000283140 650_2 $$2MeSH$$aAged
000283140 650_2 $$2MeSH$$aBiomarkers: metabolism
000283140 650_2 $$2MeSH$$aMiddle Aged
000283140 650_2 $$2MeSH$$aBrain: diagnostic imaging
000283140 650_2 $$2MeSH$$aBrain: metabolism
000283140 650_2 $$2MeSH$$aTauopathies: diagnostic imaging
000283140 650_2 $$2MeSH$$aTauopathies: metabolism
000283140 650_2 $$2MeSH$$aNeuroimaging
000283140 7001_ $$aGross, Mattes$$b1
000283140 7001_ $$aRoemer-Cassiano, Sebastian$$b2
000283140 7001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b3$$udzne
000283140 7001_ $$aDehsarvi, Amir$$b4
000283140 7001_ $$0P:(DE-2719)9001160$$aKatzdobler, Sabrina$$b5$$udzne
000283140 7001_ $$aDewenter, Anna$$b6
000283140 7001_ $$aSteward, Anna$$b7
000283140 7001_ $$aBiel, Davina$$b8
000283140 7001_ $$aHirsch, Fabian$$b9
000283140 7001_ $$0P:(DE-2719)9001652$$aGnoerich, Johannes$$b10$$udzne
000283140 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b11$$udzne
000283140 7001_ $$aStephens, Andrew W.$$b12
000283140 7001_ $$aMueller, Andre$$b13
000283140 7001_ $$aKoglin, Norman$$b14
000283140 7001_ $$aBischof, Gérard N$$b15
000283140 7001_ $$aKovacs, Gabor G.$$b16
000283140 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b17$$udzne
000283140 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b18$$udzne
000283140 7001_ $$aFranzmeier, Nicolai$$b19
000283140 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70856_104777$$gVol. 21, no. S2, p. e104777$$nS2$$pe104777$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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