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Large-scale head-to-head comparison of on- and off-target profiles of [18F]Tauvid and [18F]MK6240 tau-PET in aging and Alzheimer’s disease
Tissot C, Tsai H, Lee JY, Rahmouni N, Lussier FZ, Fonseca CS, Therriault J, Stevenson J et al.. Research Square, 2026-11-01
Topic: Plasma and spinal-fluid biomarkers
Background Tau-PET imaging enables in vivo quantification of neurofibrillary tangles, but tracers such as [ 18 F]Tauvid and [ 18 F]MK6240 present distinct affinities and off-target binding properties. Using the multicenter HEAD research cohort, a large-scale study designed to characterize the aging and Alzheimer’s disease (AD) spectrum, this study directly compares tracer performance to support harmonization across cohorts and clinical trials. Methods 681 participants underwent MRI, amyloid-β (Aβ)-PET, and tau-PET scans with both [ 18 F]Tauvid and [ 18 F]MK6240. We analyzed regions reflecting AD-related tau deposition (on-target) and known age-related or off-target binding. Analyses included paired t-tests, linear regressions, effect sizes and correlation matrices between the two tracers, across on-target and off-target regions. We further assessed tracer signal separation quantifying the noise to dynamic range ratio (NRR), where lower values indicate better assessment of tau. Results Tracers showed strong correlations in on-target regions (R = 0.81–0.95 in the whole cohort; R = 0.83–0.95 in Aβ+; R = 0.59–0.71 in Aβ-), supporting robust tau pathology detection. While off-target regions also correlated (R = 0.58–0.74 in the whole cohort; R = 0.55–0.80 in Aβ+; R = 0.57–0.73 in Aβ-), retention magnitudes differed: [ 18 F]Tauvid presented higher retention in the white matter, basal ganglia and choroid plexus, while [ 18 F]MK6240 had higher retention in the meninges and extracortical region near the entorhinal cortex. Voxelwise paired t-tests and NRR analyses, conducted at both ROI and voxelwise levels, demonstrated that [ 18 F]MK6240 consistently yielded lower NRR values across the cortex, indicating better signal separation, and potentially greater sensitivity for detecting early tau accumulation. Conclusion [ 18 F]Tauvid and [ 18 F]MK6240 capture largely overlapping patterns of tau pathology, but differ notably in the magnitude of off-target binding. These findings highlight the importance of understanding tracer similarities and differences to guide tracer selection and to improve harmonization across studies. Independent and tracer-specific optimizations of pipelines are essential before harmonization across tracers can be achieved, thereby facilitating accurate cross-study comparisons and improving clinical translation. Trial Registration: NCT05361382
Key findings
- Results Tracers showed strong correlations in on-target regions (R = 0.81–0.95 in the whole cohort; R = 0.83–0.95 in Aβ+; R = 0.59–0.71 in Aβ-), supporting robust tau pathology detection.
- Voxelwise paired t-tests and NRR analyses, conducted at both ROI and voxelwise levels, demonstrated that [ 18 F]MK6240 consistently yielded lower NRR values across the cortex, indicating better signal separation, and potentially greater sensitivity for detecting early tau accumulation.
- These findings highlight the importance of understanding tracer similarities and differences to guide tracer selection and to improve harmonization across studies.
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Study details
- Participants681
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 32 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 20 of the 62 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 681 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 20 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 20 of the 62 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Tissot, C., Tsai, H., Lee, J. Y., Rahmouni, N., Lussier, F. Z., Fonseca, C. S., et al. (2026). Large-scale head-to-head comparison of on- and off-target profiles of [18F]Tauvid and [18F]MK6240 tau-PET in aging and Alzheimer’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-9987995/v1
Vancouver
Tissot C, Tsai H, Lee JY, Rahmouni N, Lussier FZ, Fonseca CS, et al. Large-scale head-to-head comparison of on- and off-target profiles of [18F]Tauvid and [18F]MK6240 tau-PET in aging and Alzheimer’s disease. Research Square. 2026. doi:10.21203/rs.3.rs-9987995/v1.
BibTeX
@article{tissot2026-2c13a0a9,
author = {Tissot, C. and Tsai, H. and Lee, J. Y. and Rahmouni, N. and Lussier, F. Z. and Fonseca, C. S. and Therriault, J. and Stevenson, J. and others},
title = {{Large-scale head-to-head comparison of on- and off-target profiles of [18F]Tauvid and [18F]MK6240 tau-PET in aging and Alzheimer’s disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-9987995/v1},
url = {https://doi.org/10.21203/rs.3.rs-9987995/v1}
}