Toward harmonizing quantification of dopamine neuron imaging biomarkers in Parkinson's disease: the centamine scale
Author(s)
Type
Journal Article
Abstract
Objective
Dopaminergic imaging is a key biomarker for both the investigation of the biology of Parkinson's disease and related synucleinopathies and the evaluation of potential therapies in clinical trials. This work presents a harmonized approach for quantifying dopaminergic molecular imaging tracers, such as [123I]ioflupane (dopamine transporter scan [DaTscan]) single photon emission computed tomography (SPECT) and [18F]AV133 positron emission tomography (PET), which assess dopaminergic neuronal loss. The proposed method aims to standardize regional outcome measures using a unified scale called Centamines.
Methods
The Centamines framework comprises 3 analysis levels. Level 1 defines the Centamine scale based on healthy subject data from [123I]ioflupane SPECT (n = 224). Level 2 uses head-to-head data between Tracer X and [123I]ioflupane SPECT to map Tracer X onto the Centamine scale. Level 3 maps additional tracers using prior mappings. A level 2 analysis was performed using [123I]ioflupane SPECT and [18F]AV133 PET data (n = 68) to convert [18F]AV133 PET into Centamines.
Results
Level 1 successfully established the Centamine scale using healthy [123I]ioflupane SPECT scans. Level 2 revealed moderate-strong linear correlations (R2 = 0.51–0.83) between [123I]ioflupane SPECT and [18F]AV133 PET across 5 brain regions. Mapped Centamine values showed minimal differences between tracers, ranging from 1.5% (post-commissural putamen) to 3% (caudate).
Interpretation
The Centamine scale holds promise for the harmonized quantification of dopaminergic neuronal imaging markers. The Centamine strategy would enable and accelerate clinical trials in Parkinson's disease using dopaminergic imaging outcomes.
Dopaminergic imaging is a key biomarker for both the investigation of the biology of Parkinson's disease and related synucleinopathies and the evaluation of potential therapies in clinical trials. This work presents a harmonized approach for quantifying dopaminergic molecular imaging tracers, such as [123I]ioflupane (dopamine transporter scan [DaTscan]) single photon emission computed tomography (SPECT) and [18F]AV133 positron emission tomography (PET), which assess dopaminergic neuronal loss. The proposed method aims to standardize regional outcome measures using a unified scale called Centamines.
Methods
The Centamines framework comprises 3 analysis levels. Level 1 defines the Centamine scale based on healthy subject data from [123I]ioflupane SPECT (n = 224). Level 2 uses head-to-head data between Tracer X and [123I]ioflupane SPECT to map Tracer X onto the Centamine scale. Level 3 maps additional tracers using prior mappings. A level 2 analysis was performed using [123I]ioflupane SPECT and [18F]AV133 PET data (n = 68) to convert [18F]AV133 PET into Centamines.
Results
Level 1 successfully established the Centamine scale using healthy [123I]ioflupane SPECT scans. Level 2 revealed moderate-strong linear correlations (R2 = 0.51–0.83) between [123I]ioflupane SPECT and [18F]AV133 PET across 5 brain regions. Mapped Centamine values showed minimal differences between tracers, ranging from 1.5% (post-commissural putamen) to 3% (caudate).
Interpretation
The Centamine scale holds promise for the harmonized quantification of dopaminergic neuronal imaging markers. The Centamine strategy would enable and accelerate clinical trials in Parkinson's disease using dopaminergic imaging outcomes.
Date Issued
2026-04-01
Date Acceptance
2025-12-02
Citation
Annals of Neurology, 2026, 99 (4), pp.949-963
ISSN
0364-5134
Publisher
Wiley
Start Page
949
End Page
963
Journal / Book Title
Annals of Neurology
Volume
99
Issue
4
Copyright Statement
© 2026 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41556298
Subjects
Humans
Parkinson Disease
Tomography, Emission-Computed, Single-Photon
Male
Dopaminergic Neurons
Female
Biomarkers
Nortropanes
Positron-Emission Tomography
Middle Aged
Aged
Brain
Adult
Dopamine Plasma Membrane Transport Proteins
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2026-01-20