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

Objective: Dopaminergic imaging is a key biomarker for both the investigation of 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 (DaTscan) SPECT and [18F]AV133 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 three 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 (R^2 = 0.44 - 0.78) between [123I]ioflupane SPECT and [18F]AV133 PET across five 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 utilizing dopaminergic imaging outcomes.