Tau positron emission tomography harmonization using the CenTauR approach: General conversion equations, relevant cut-points, and external validation

Tau positron emission tomography (PET) tracers differ in kinetics, binding properties, and quantification pipelines, complicating cross-study comparisons. The CenTauR approach provides a unified framework for harmonizing tau PET quantification across tracers.

We defined a tracer-agnostic "Standard Method" using Statistical Parametric Mapping 12, standardized regions of interest, and harmonized acquisition parameters. Using data from five tau tracers-[¹⁸F]flortaucipir, [¹⁸F]MK-6240, [¹⁸F]PI-2620, [¹⁸F]RO948, and [¹⁸F]GTP1-we applied the Joint Propagation Model to derive linear equations converting regional standardized uptake value ratios into the tracer-independent CenTauR scale. Validation included independent cross-sectional, longitudinal, and test-retest datasets across multiple cohorts.

The CenTauR scale yielded highly consistent regional values across tracers, with strong cross-tracer agreement and robust performance in external validation cohorts. We also expressed clinically relevant cut-points and staging boundaries on the CenTauR scale.

The CenTauR approach enables harmonized, tracer-independent quantification of tau PET, supporting reproducibility across studies and improving interpretation in clinical research and multicenter trials.