This is a summary of Gnörich J et al. Dynamic [¹⁸F]PI-2620 recording facilitates prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration; Mol Neurodegener. https://doi.org/10.1186/s13024-026-00997-3

The challenge

Alzheimer’s disease and related neurodegenerative disorders can involve overlapping clinical symptoms but different underlying molecular pathologies. The A/T/N framework distinguishes amyloid, tau and neurodegeneration, yet these components are commonly assessed with separate imaging methods, including amyloid-PET, tau-PET and FDG-PET. This can make comprehensive molecular characterization more complex, time-consuming and resource-intensive. The tau tracer [¹⁸F]PI-2620 is already used to visualize tau pathology, but its dynamic uptake over time may contain additional information beyond conventional measures of tau burden. The researchers therefore asked whether a single dynamic PI-2620 PET acquisition could provide information on amyloid status, regional tau pathology and neurodegeneration at the same time.

Our approach

The researchers studied 129 patients with tauopathies and 17 healthy controls using 60-minute dynamic [¹⁸F]PI-2620 PET. Kinetic modelling generated three complementary measures: K2a to predict β-amyloid status, DVR to quantify regional tau burden, and R1 as a marker of neurodegeneration. The results were compared with amyloid-PET, FDG-PET, MRI and cerebrospinal fluid biomarkers, and amyloid prediction was additionally tested in an independent cohort of 97 individuals.

Our findings

Dynamic [¹⁸F]PI-2620 PET distinguished β-amyloid-positive 3/4-repeat tauopathies from β-amyloid-negative 4-repeat tauopathies, including cases with little or no visually detectable tau signal. K2a predicted amyloid status with an AUC of 0.99 in the main cohort and 0.98 in the independent validation cohort. DVR captured distinct cortical and subcortical tau patterns, while R1 closely reflected established markers of neurodegeneration. Combining these measures enabled individualized three-dimensional A/T/N staging from one scan.

The implications

Dynamic [¹⁸F]PI-2620 PET could provide a more streamlined way to characterize amyloid, tau and neurodegeneration in a single imaging session, supporting personalized disease profiling and potentially reducing the need for multiple scans.

Creating SyNergies

The study was led by Günter Höglinger, Nicolai Franzmeier, and Matthias Brendel and involved other SyNergy members. Their collaboration combined expertise in nuclear medicine, neurology and systems neurobiology to advance molecular imaging.