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Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue
Aguero C, Dhaynaut M, Normandin MD, Amaral AC, Guehl NJ, Neelamegam R, Marquie M, Johnson KA et al.. Acta neuropathologica communications, 2019-03-11
Topic: Brain proteins, microglia and lab models
[F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease. We have examined regional and substrate-specific binding patterns as well as possible off-target binding of this tracer on human brain tissue to advance towards its validation. We applied [F-18]-MK-6240 phosphor screen and high resolution autoradiography to postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau (Pick's disease, progressive supranuclear palsy and corticobasal degeneration), chronic traumatic encephalopathy, frontotemporal lobar degeneration-Tar DNA-binding protein 43 (TDP-43), dementia with Lewy bodies, cerebral amyloid angiopathy and elderly controls free of pathologic changes of neurodegenerative disease. We also directly compared the binding properties of [F-18]-MK-6240 and [F-18]-AV-1451 in human tissue, and examined potential nonspecific binding of both tau tracers to monoamine oxidases (MAO) by using autoradiography in the presence of selective monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitors. Our data indicate that MK-6240 strongly binds to neurofibrillary tangles in Alzheimer disease but does not seem to bind to a significant extent to tau aggregates in non-Alzheimer tauopathies, suggesting that it may have a limited utility for the in vivo detection of these pathologies. There is no evidence of binding to lesions containing β-amyloid, α-synuclein or TDP-43. In addition, we identified MK-6240 strong off-target binding to neuromelanin and melanin-containing cells, and some weaker binding to areas of hemorrhage. These binding patterns are nearly identical to those previously reported by our group and others for [F-18]-AV-1451. Of note, [F-18]-MK-6240 and [F-18]-AV-1451 autoradiographic binding signals were only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline, suggesting that MAO enzymes do not appear to be a significant binding target of any of these two tracers. Together these novel findings provide relevant insights for the correct interpretation of in vivo [F-18]-MK-6240 PET imaging.
Key findings
- Our data indicate that MK-6240 strongly binds to neurofibrillary tangles in Alzheimer disease but does not seem to bind to a significant extent to tau aggregates in non-Alzheimer tauopathies, suggesting that it may have a limited utility for the in vivo detection of these pathologies.
- Of note, [F-18]-MK-6240 and [F-18]-AV-1451 autoradiographic binding signals were only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline, suggesting that MAO enzymes do not appear to be a significant binding target of any of these two tracers.
Why it matters
In postmortem brain tissue, the tau PET tracer MK-6240 bound strongly to tangles in Alzheimer disease but not much to tau aggregates in other tau-related diseases. This is a laboratory validation study of a imaging tool, not a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 2 / 5 | 2019 — within 10 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 173 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.2 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 10.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 72 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Teresa Gómez‐Isla: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30857558) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
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Read the original
- DOI: 10.1186/s40478-019-0686-6
- PubMed: 30857558
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Aguero, C., Dhaynaut, M., Normandin, M. D., Amaral, A. C., Guehl, N. J., Neelamegam, R., et al. (2019). Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta neuropathologica communications. https://doi.org/10.1186/s40478-019-0686-6
Vancouver
Aguero C, Dhaynaut M, Normandin MD, Amaral AC, Guehl NJ, Neelamegam R, et al. Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta neuropathologica communications. 2019. doi:10.1186/s40478-019-0686-6. PMID: 30857558.
BibTeX
@article{aguero2019-30857558,
author = {Aguero, C. and Dhaynaut, M. and Normandin, M. D. and Amaral, A. C. and Guehl, N. J. and Neelamegam, R. and Marquie, M. and Johnson, K. A. and others},
title = {{Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue}},
journal = {Acta neuropathologica communications},
year = {2019},
doi = {10.1186/s40478-019-0686-6},
pmid = {30857558},
url = {https://doi.org/10.1186/s40478-019-0686-6}
}
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