Biological Factors Influencing [18F]MK6240 and [18F]FTP Correlation in Target Regions
Bibliographic record
Abstract
Abstract Background The association between [18F]Flortaucipir (FTP) and [18F]MK6240, two commonly used tau‐PET tracers in Alzheimer’s disease (AD), varies due to distinct binding properties and off‐target signal regions. Our study aims to elucidate the biological factors influencing this association and evaluate the applicability of a common equation across different on‐target regions. Method 113 individuals from the HEAD dataset (11 young, 58 cognitively unimpaired elderly, and 44 cognitively impaired) underwent [18F]MK6240, [18F]FTP and Aβ‐PET scans. Images were processed using the inferior cerebellar grey (CG) as the reference region, with subjects categorized by Aβ status. Stepwise linear fitting identified off‐target (OFF) regions impacting tracer associations within the whole cortex, Braak and temporal‐meta regions of interest (ROIs). OFF regions included were a composite mask (pallidum, putamen, caudate ‐ PPC) to address collinearity in subcortical nuclei, as well as the region with the greatest partial volume effects (PVE) on the ROI (meninges, choroid plexus, and the hotspot medial to entorhinal cortices (EC)). Akaike information criteria (AIC) analyses tested linear models with various off‐target regions. Result PPC and PVE regions influenced tracer association in on‐target regions. PPC binding is associated with age. PPC and meninges retention, along with Aβ status interaction, demonstrated the best model fit for the whole cortex (Figure 1). Weighting factors derived from the whole cortex model were applied to Braak regions and temporal meta‐ROI. Braak III‐VI and temporal‐meta ROI showed optimal models including OFF regions and Aβ status interaction (Figure 2). Forcing the whole equation gave optimal results. For Braak I (EC), adding the OFF covariates only was the best model. For Braak II (hippocampus), the best model included OFF regions and the interaction with Aβ status (Figure 2). Forcing the whole cortex equation onto Braak I and Braak II yielded suboptimal fits. Conclusion Harmonizing tau‐PET tracers involves considering significant covariates. Integrating meningeal and age‐related off‐target regions enhances [18F]MK6240 and [18F]FTP association in on‐target regions, further improved by Aβ status inclusion. While the whole cortex model may not suit early ROI, it proves effective for Braak III and beyond. Creating an equation for tracer translation necessitates incorporating meningeal and subnuclei off‐target retention.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".