Toward Harmonizing Quantification of Dopamine Neuron Imaging Biomarkers in Parkinson's Disease: The Centamine Scale

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.

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.

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).

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. ANN NEUROL 2026;99:949-963.