# Alpha-synuclein PET: works for MSA, not for Parkinson's

Source: https://nuclide.cc/opportunities/opp-alpha-synuclein-pet-parkinsons/  
Nuclide record `opp-alpha-synuclein-pet-parkinsons` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Parkinson's disease is defined by a protein clumping in the brain, and no scan can see it. The first tracer to reach patients does light up a rarer, related disease but not Parkinson's itself, while a spinal-fluid test already identifies Parkinson's with high accuracy.

## Summary

Amyloid and tau both have approved PET agents. Alpha-synuclein, the protein that defines Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, has none: no small molecule targeting misfolded alpha-synuclein has been approved by the FDA as a PET radiopharmaceutical. The clinical consequence is that early Parkinson's cannot be separated from multiple system atrophy or progressive supranuclear palsy when the picture is ambiguous, and no anti-alpha-synuclein drug programme can show target engagement in a living brain.

The most advanced agent is [18F]ACI-12589 from AC Immune, with a 42-participant published dataset in Nature Communications in 2023: 8 healthy controls, 8 Parkinson's, 2 dementia with Lewy bodies, 13 multiple system atrophy, 3 progressive supranuclear palsy, 5 Alzheimer's and 3 hereditary ataxias. The result is a genuine partial success and a genuine partial failure. Binding statistically separated multiple system atrophy patients from controls and from other neurodegenerative disorders, with clear signal in cerebellar white matter and middle cerebellar peduncles, but limited binding in Parkinson's disease; a conference report put it more bluntly, that PET signals were undetectable in other synucleinopathies despite the tracer binding post-mortem tissue from those same disorders.

Meanwhile the non-imaging competitor has already won the diagnostic question for Parkinson's. Seed amplification assays on cerebrospinal fluid are reported at 87.7% sensitivity and 96.3% specificity for Parkinson's in the PPMI cohort, with a pooled meta-analysis at 0.86 and 0.92. What the assay cannot do is say where in the brain the pathology is, or how much, or whether a drug reduced it, and it is markedly less reliable in multiple system atrophy. That is the residual space an imaging agent has.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: a-synuclein PET; ACI-12589
- Tags: unmet need first; neurology; worked negative; pharmacodynamic marker

## Sources

- [18F]ACI-12589 first-in-human, Nature Communications 2023: https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/
- Conference report: signal only in multiple system atrophy: https://www.alzforum.org/news/conference-coverage/first-field-synuclein-pet-only-multiple-system-atrophy
- No approved small-molecule alpha-synuclein PET agent: https://pmc.ncbi.nlm.nih.gov/articles/PMC13121216/
- Seed amplification assays: past, present and future roles: https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm
- Pooled meta-analysis of alpha-synuclein seed amplification assays: https://pmc.ncbi.nlm.nih.gov/articles/PMC12192484/

## Connected records

- isotopes: [Fluorine-18](https://nuclide.cc/isotopes/f-18/)
- targets: [Alpha-synuclein](https://nuclide.cc/targets/alpha-synuclein/), [Amyloid beta plaques](https://nuclide.cc/targets/amyloid-beta/), [Dopamine transporter (DAT)](https://nuclide.cc/targets/dopamine-transporter/), [Tau protein (neurofibrillary tangles)](https://nuclide.cc/targets/tau-protein/)
- indications: [Parkinsonian syndromes](https://nuclide.cc/indications/parkinsonian-syndromes/)
- technologies: [PET (positron emission tomography)](https://nuclide.cc/technologies/pet/), [PET/CT](https://nuclide.cc/technologies/pet-ct/)
- drugs: [Ioflupane I-123](https://nuclide.cc/drugs/i-123-ioflupane/)

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