Journal Article

DZNE-2026-01004

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dynamic [18F]PI-2620 recording facilitates prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration.

Gnörich, J. (First author)DZNE* ; Kusche-Palenga, J. ; Kling, A. ; Dehsarvi, A. ; Bronte, A. ; Frontzkowski, L. ; Zatcepin, A.DZNE* ; Zaganjori, M. ; Schöberl, F. ; Roemer-Cassiano, S. N. ; Rauchmann, B.-S.Extern* ; Kurz, C. ; Palleis, C.DZNE* ; Bernhardt, A. M.DZNE* ; Jäck, A.DZNE* ; Katzdobler, S.DZNE* ; Scheifele, M. ; Bauer, T. ; Bischof, G. N. ; Eimeren, T.Extern* ; Drzezga, A.DZNE* ; Häckert, J. ; Perneczky, R.DZNE* ; Rullmann, M. ; Bürger, K.Extern* ; Werner, R. A. ; Zwergal, A. ; Levin, J.DZNE* ; Bartenstein, P. ; Sabri, O.Extern* ; Barthel, H. ; Stöcklein, S.Extern* ; Höglinger, G.DZNE* ; Franzmeier, N. ; Brendel, M. (Last author)DZNE*

2026
Biomed Central London

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Please use a persistent id in citations: doi:10.1186/s13024-026-00997-3

Abstract: Patients with Alzheimer's disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, A/T/N assessment incorporates β-amyloid-PET (A), tau-PET (T), and [18F]FDG-PET (N). We evaluated if dynamic features of tau-PET with [18F]PI-2620 allow prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration in individual patients using a single imaging session.We studied 129 patients with tauopathies, comprising 47 patients with β-amyloid-positive 3/4-repeat tauopathy and 82 patients with β-amyloid-negative primary 4-repeat tauopathies, alongside 17 healthy controls. Participants underwent 60-minute dynamic [18F]PI-2620 tau-PET. Kinetic modelling simultaneously provided tracer efflux rate (K2a) as a predictor for β-amyloid status, distribution volume ratio (DVR) for regional tau burden, and relative perfusion (R1) as a marker of neurodegeneration. These parameters were validated against β-amyloid-PET, [18F]FDG-PET, volumetric MRI, and cerebrospinal fluid biomarkers using receiver operating characteristic and correlation analyses and visual assessments. [18F]PI-2620K2a-based prediction of β-amyloid positivtiy was additionally tested in an independent, clinically heterogeneous validation cohort of 97 individuals.[18F]PI-2620K2a differentiated tau isoform compositions despite clinically overlapping presentations and tau-PET patterns, demonstrating reduced cortical tracer clearance in 3/4-repeat compared with 4-repeat tauopathies. [18F]PI-2620K2a remained sensitive in individuals with visually negative or low [18F]PI-2620DVR signals and outperformed both tau burden and perfusion for predicting β-amyloid status, achieving an area under the curve of 0.99, a positive predictive value of 91.5%, and a negative predictive value of 95.1%. Performance remained robust in the independent validation cohort, with an area under the curve of 0.98, a positive predictive value of 87.9%, and a negative predictive value of 95.3%. [18F]PI-2620DVR quantified regional tau patterns, with cortical predominance in 3/4-repeat tauopathy and subcortical involvement in 4-repeat tauopathies. [18F]PI-2620R1 exhibited strong quantitative and visual associations with established markers of neurodegeneration. Integration of K2a, DVR, and R1 in disease-specific composite regions enabled individualized three-dimensional A/T/N staging.Dynamic [18F]PI-2620 PET imaging facilitates assessment of the β-amyloid status and regional staging of tau and neurodegeneration during a single acquisition. This one-stop-shop approach may reduce radiation exposure, streamline diagnostic workflows, and facilitate personalized disease profiling.

Keyword(s): Humans (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Female (MeSH) ; Tauopathies: diagnostic imaging (MeSH) ; Tauopathies: metabolism (MeSH) ; Male (MeSH) ; Aged (MeSH) ; tau Proteins: metabolism (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Middle Aged (MeSH) ; Brain: metabolism (MeSH) ; Biomarkers (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Neurodegenerative Diseases: diagnostic imaging (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Fluorine Radioisotopes (MeSH) ; Pyridines (MeSH) ; A/T/N ; Dynamic imaging ; Staging ; Tau-PET ; Tauopathies ; β-amyloid ; Amyloid beta-Peptides ; tau Proteins ; ((18)F)PI-2620 ; Biomarkers ; PI-2620 ; Fluorine Radioisotopes ; Pyridines

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)
2. Clinical Research (Munich) (Clinical Research (Munich))
3. Positron Emissions Tomography (PET) (AG Boecker)
4. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
5. Clinical Neurodegeneration (AG Levin)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

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