Home › Research › Brain tissue and pathology
Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology
Efthymia Vokali, Elodie Chevalier, Nicolas Dreyfus, Dorian Charmey, Tania Melly, Jacqueline Kocher, Monisha Ratnam, Andreia M. Serra et al.. Nature Communications, 2025-10-24
Topic: Brain proteins, microglia and lab models
Aggregated TDP-43 is a hallmark of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and limbic-predominant age-related TDP-43 encephalopathy (LATE), and a common co-pathology in other neurodegenerative diseases. Currently, no specific biomarkers exist to assess TDP-43 pathology in vivo. We developed two small-molecule radiopharmaceuticals, [18F]ACI-19278 and [18F]ACI-19626, for visualizing TDP-43 inclusions by positron emission tomography (PET). Both ligands bind with high affinity to aggregated, but not soluble, TDP-43 in patient brain samples from diverse TDP-43 proteinopathies, including frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), ALS, and LATE, and in cell models. Both compounds display excellent selectivity for TDP-43 over Aβ, Tau, and α-synuclein aggregates. In non-human primates, [18F]ACI-19278 and [18F]ACI-19626 show a pharmacokinetic profile suitable for brain PET imaging (rapid brain uptake; fast and complete washout). ACI-19278 and ACI-19626 are promising first-in-class TDP-43 PET tracers with the potential to revolutionize the diagnosis and treatment of neurodegenerative proteinopathies, enabling a precision medicine approach. High-affinity ligands were developed that specifically bind aggregated TDP-43, are selective over common co-pathologies, and possess pharmacokinetic profiles suitable for PET imaging to visualize TDP-43 pathology in the brains of patients.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Vokali, E., Chevalier, E., Dreyfus, N., Charmey, D., Melly, T., Kocher, J., et al. (2025). Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology. Nature Communications. https://doi.org/10.1038/s41467-025-64540-6
Vancouver
Vokali E, Chevalier E, Dreyfus N, Charmey D, Melly T, Kocher J, et al. Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology. Nature Communications. 2025. doi:10.1038/s41467-025-64540-6. PMID: 41136425.
BibTeX
@article{vokali2025-41136425,
author = {Vokali, Efthymia and Chevalier, Elodie and Dreyfus, Nicolas and Charmey, Dorian and Melly, Tania and Kocher, Jacqueline and Ratnam, Monisha and Serra, Andreia M. and others},
title = {{Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology}},
journal = {Nature Communications},
year = {2025},
doi = {10.1038/s41467-025-64540-6},
pmid = {41136425},
url = {https://doi.org/10.1038/s41467-025-64540-6}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Both ligands bind with high affinity to aggregated, but not soluble, TDP-43 in patient brain samples from diverse TDP-43 proteinopathies, including frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), ALS, and LATE, and in cell models.
- Both compounds display excellent selectivity for TDP-43 over Aβ, Tau, and α-synuclein aggregates.
- In non-human primates, [18F]ACI-19278 and [18F]ACI-19626 show a pharmacokinetic profile suitable for brain PET imaging (rapid brain uptake; fast and complete washout).
- ACI-19278 and ACI-19626 are promising first-in-class TDP-43 PET tracers with the potential to revolutionize the diagnosis and treatment of neurodegenerative proteinopathies, enabling a precision medicine approach.
- High-affinity ligands were developed that specifically bind aggregated TDP-43, are selective over common co-pathologies, and possess pharmacokinetic profiles suitable for PET imaging to visualize TDP-43 pathology in the brains of patients.
Why it matters
Two new radiopharmaceuticals were developed that bind aggregated TDP-43 with high affinity and show selectivity over Aβ, tau and α-synuclein aggregates, with suitable brain imaging profiles in non-human primates. These are candidate PET imaging tracers for diagnosis, not a treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 49/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 12.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tamara S. Seredenina: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Erasmus MC: institution h-index 1,321 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41136425) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-025-64540-6
- PubMed: 41136425
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 18.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Brain tissue and pathology
Also tagged “machine”
834 studies in the library carry the topic tag “machine”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 834 tagged studies.