Synuclein PET tracers

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Makoto Higuchi's group at Japan's National Institutes for Quantum Science and Technology (QST) with colleagues (C05-05; Endo et al., Neuron, 2024); Oskar Hansson's team at Lund with AC Immune (ACI-12589; Smith et al., Nature Communications, 2023, which lists funding from Wallenberg, the Swedish Research Council, the Michael J. Fox Foundation and others); the German company MODAG with university and Max Planck groups ([11C]MODAG-005; Saw et al., Science Translational Medicine, 2026, funded by the Foundation, Carl-Zeiss-Stiftung, EU Horizon 2020, DFG and MODAG).

What happened

The Michael J. Fox Foundation announced a $2 million prize in June 2016 for the first selective alpha-synuclein PET tracer, a radioactive dye that lights up clumps in a scan. The target is hard: the clumps are small, mostly inside cells, and sit beside amyloid and tau.

In October 2023 AC Immune and Lund reported [18F]ACI-12589 (23 people with synuclein disorders, 11 with other neurodegenerative diseases, 8 controls). Binding was clear in the cerebellar white matter of multiple system atrophy (MSA), a related disease with heavy synuclein deposits, and limited in Parkinson's. On 5 June 2024 Neuron published [18F]C05-05 (a modified tau tracer): in 10 people with Parkinson's or dementia with Lewy bodies it stayed high in the midbrain, and the signal tracked motor severity; 8 controls and 3 MSA patients were also scanned. In December 2025 MODAG said its tracers had initial human images in MSA and Parkinson's. The first-in-human data for [11C]MODAG-005 then appeared in Science Translational Medicine in 2026: binding in regions affected by synuclein in patients with MSA and with Parkinson's, though the abstract does not give numbers or say how well it separates patients from controls.

Separately, MJFF's Ken Griffin Alpha-synuclein Imaging Competition, funded largely by a $7.5 million gift from Ken Griffin, awarded a combined $8.5 million in 2020 to three teams: AC Immune, Mass General Brigham and Merck (MJFF, which dates it 30 July 2020; the MJFF 2020 Year in Review says August). No per-team split is given.

On 30 May 2024 the Foundation also announced $9.75 million for five quantitative-biomarker teams, two of them PET: Invicro with Higuchi, and Merck (MJFF release). The Foundation describes the competition as a three-year, $10 million programme begun in 2019. In March 2023 it named Merck the winner, with an extra $1.5 million; AC Immune and Mass General Brigham were runners-up. A separate $2 million Alpha-synuclein Imaging Prize remained open to the first team to show clinical evidence for a tracer and share it. By 2024 all three finalists were testing tracers in people, with Foundation funding for the Mass General Brigham and Merck trials and first results expected in 2025 (MJFF 2023 Year in Review; MJFF 2024 Year in Review).

Why it moved us toward a cure

A scan of the target would show whether an anti-synuclein drug (landmark 63, landmark 29) actually reduces clumps. The seed assay (landmark 9) shows whether misfolded synuclein is present but not how much, or where.

Outcome

Open and unproven for Parkinson's. A 2025 review found C05-05 the only tracer reported to detect it; MODAG-005's 2026 report adds a second. Critics note the overlap between patient and control uptake is large (Hansson: "far too great" for diagnosis), the tracer also binds tau and amyloid, and there is no independent replication. The brain-penetration, light sensitivity and small-sample problems remain.

Sources

• MJFF 2023 Year in Review; MJFF 2024 Year in Review (funding facts only)
• MJFF: three teams win Ken Griffin Alpha-synuclein Imaging Competition, 2020
• Alzforum on Endo et al., Neuron, 2024 · QST release (DOI 10.1016/j.neuron.2024.05.006, PMID 38843838; no correction listed)
• Smith et al., Nat Commun 2023, DOI 10.1038/s41467-023-42305-3 · Saw et al., Sci Transl Med 2026, DOI 10.1126/scitranslmed.aec0813 (abstracts read via Europe PMC)
• ClinicalTrials.gov NCT06891703: AC Immune Phase 1 of [18F]ACI-15916, recruiting, started 20 Mar 2025, primary completion estimated Mar 2026
• AC Immune release, 27 Oct 2023
• MJFF prize announcement, 2016
• Ni, Neural Regen Res 2025 review · MODAG/MJFF grant, 17 Dec 2025 (company claims only)
• Not yet verified: the $2 million Alpha-synuclein Imaging Prize (no award announcement found, 20 Oct 2026); results from ACI-15916 or the Merck and Mass General Brigham tracers; MODAG-005's full 2026 numbers.