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

**Authors:** Zhen Fan, Graham Searle, Gaia Rizzo, Justin Albani, Patrick Cella, Robert Comley, Gregory Klein, Luca Passamonti, Cristian Salinas, Adam J. Schwarz, Leonardo Iaccarino, Gilles Tamagnan, Jamie Eberling, Ken Marek, John Seibyl, Roger N. Gunn, Kenneth Marek, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana Chahine, Christopher Coffey, Kalpana Merchant, Kathleen Poston, Roseanne Dobkin, Tatiana Foroud, Brit Mollenhauer, Dan Weintraub, Ethan Brown, Karl Kieburtz, Mark Frasier, Todd Sherer, Sohini Chowdhury, Roy Alcalay, Aleksandar Videnovic, Duygu Tosun‐Turgut, Werner Poewe, Susan Bressman, Jan Hammer, Raymond James, Ekemini Riley, John Seibyl, Leslie Shaw, David Standaert, Sneha Mantri, Nabila Dahodwala, Michael Schwarzschild, Connie Marras, Hubert Fernandez, Ira Shoulson, Helen Rowbotham, Paola Casalin, Claudia Trenkwalder, Todd Sherer, Sohini Chowdhury, Mark Frasier, Jamie Eberling, Katie Kopil, Alyssa O'Grady, Maggie McGuire Kuhl, Leslie Kirsch, Tawny Willson, Charles Adler, Roy Alcalay, Amy Amara, Paolo Barone, Bastiaan Bloem, Susan Bressman, Kathrin Brockmann, Norbert Brüggemann, Lana Chahine, Kelvin Chou, Nabila Dahodwala, Alberto Espay, Stewart Factor, Hubert Fernandez, Michelle Fullard, Douglas Galasko, Robert Hauser, Penelope Hogarth, Shu‐Ching Hu, Michele Hu, Stuart Isaacson, Christine Klein, Rejko Krueger, Mark Lew, Zoltan Mari, Connie Marras, Maria Jose Martí, Nikolaus McFarland, Tiago Mestre, Brit Mollenhauer, Emile Moukheiber, Alastair Noyce, Njideka Okubadejo, Sarah O'Shea, Rajesh Pahwa, Nicola Pavese, Werner Poewe, Ron Postuma, Giulietta Riboldi, Lauren Ruffrage, Javier Ruiz Martinez, David Russell, Marie H Saint‐Hilaire, Neil Santos, Wesley Schlett47, Ruth Schneider, Holly Shill, David Shprecher, Tanya Simuni, David Standaert, Leonidas Stefanis, Yen Tai, Caroline Tanner, Arjun Tarakad, Eduardo Tolosa PhD34, Aleksandar Videnovic, Susan Ainscough, Courtney Blair, Erica Botting, Isabella Chung, Kelly Clark, Ioana Croitoru, Kelly DeLano, Iris Egner, Fahrial Esha, May Eshel, Frank Ferrari, Victoria Kate Foster, Alicia Garrido, Madita Grümmer, Bethzaida Herrera, Ella Hilt, Chloe Huntzinger, Raymond James, Farah Kausar, Christos Koros, Yara Krasowski60, Dustin Le, Ying Liu, Taina M. Marques, Helen Mejia Santana, Sherri Mosovsky, Jennifer Mule, Philip Ng, Lauren O'Brien, Abiola Ogunleye, Oluwadamilola Ojo, Obi Onyinanya, Lisbeth Pennente, Romina Perrotti, Michael Pileggi, Ashwini Ramachandran, Deborah Raymond, Jamil Razzaque, Shawna Reddie, Kori Ribb, Kyle Rizer, Janelle Rodriguez, Stephanie Roman, Clarissa Sanchez, Cristina Simonet, Anisha Singh, Elisabeth Sittig, Barbara Sommerfeld, Angela Stovall, Bobbie Stubbeman, Alejandra Valenzuela, Catherine Wandell, Diana Willeke, Karen Williams, Dilinuer Wubuli

PMC · DOI: 10.1002/ana.78116 · Annals of Neurology · 2026-01-20

## TL;DR

This paper introduces a standardized scale called Centamines to harmonize dopamine neuron imaging measurements in Parkinson's disease, enabling better clinical research.

## Contribution

The novel Centamines framework provides a unified scale for quantifying dopaminergic imaging biomarkers across different tracers.

## Key findings

- The Centamine scale was successfully established using healthy [123I]ioflupane SPECT scans.
- Mapped Centamine values showed minimal differences between [123I]ioflupane SPECT and [18F]AV133 PET tracers.
- Linear correlations between tracers ranged from moderate to strong (R² = 0.51–0.83) across brain regions.

## Abstract

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 (R
2 = 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

## Linked entities

- **Chemicals:** [123I]ioflupane (PubChem CID 3086674), [18F]AV133 (PubChem CID 17755050)
- **Diseases:** Parkinson's disease (MONDO:0005180)

## Full-text entities

- **Genes:** SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531] {aka DAT, DAT1, PKDYS, PKDYS1}
- **Diseases:** Parkinson's Disease (MESH:D010300), synucleinopathies (MESH:D000080874), dopaminergic neuronal loss (MESH:D009410)
- **Chemicals:** [18F]AV133 (MESH:C549477), DaTscan (MESH:C519528), Dopamine (MESH:D004298), Tracer X (-)

## Full text

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC13011789/full.md

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Source: https://tomesphere.com/paper/PMC13011789