Utility of [18F]PI-2620 as Universal Biomarker for the Amyloid/Tau/Neurodegeneration Classification of Alzheimer Disease: An Exploratory Study with Dual-Phase PET Imaging.

BACKGROUND AND PURPOSE: Our purpose was to identify spatial covariance patterns of dual-phase [18F]PI-2620 PET in biomarker-confirmed Alzheimer disease (AD) and healthy control subjects by applying data-driven multivariate analysis to multimodality neuroimaging data. We also tested the ability of pattern expression values in individual subjects to predict amyloid status and evaluate the efficacy of [18F]PI-2620 as a single, universal biomarker for the amyloid/tau/neurodegeneration (A/T/N) classification. MATERIALS AND METHODS: Twenty-five subjects (15 men, 10 women, mean age: 64.5 ± 10.1, range 51-89) including 15 with amyloid-positive AD and 10 amyloid-negative healthy controls were analyzed. Brain PET images of dual-phase [18F]PI-2620 (early-phase for cerebral perfusion; late-phase for tau pathology) and late-phase [18F]florbetaben for amyloid pathology were acquired in each participant alongside high-resolution brain MRI. PET images were converted into maps of standard uptake value ratio by using cerebellar GM as reference region. Spatial covariance analysis was performed separately in the standard brain space by using a well-established computing toolbox in the public domain. RESULTS: We identified distinct Alzheimer disease-related patterns (ADRP) of spatial covariance capturing prominent abnormal features in brain amyloid, tau, and perfusion (ADRP-amyloid, ADRP-tau, and ADRP-perfusion) underlying this disease. There was some overlap among these topographies particularly between ADRP-tau and ADRP-amyloid. ADRP expression scores of each pattern differentiated AD from healthy controls (P < .0001) with group discriminant analysis yielding an accuracy of 96% in predicting amyloid status with the combination of ADRP-tau and ADRP-perfusion scores. These scores correlated positively among themselves and with several clinical measures of disease severity in the combined subject group. CONCLUSIONS: Analysis of AD and normal controls suggests a potential role of [18F]PI-2620 as a single biomarker for the A/T/N classification.