Evaluation of Tau Radiotracers in Chronic Traumatic Encephalopathy
Bibliographic record
Abstract
Chronic traumatic encephalopathy (CTE) is a neurologic disorder associated with head injuries, diagnosed by the perivascular accumulation of hyperphosphorylated tau protein (phospho-tau) identified at autopsy. Tau PET radiopharmaceuticals developed for imaging Alzheimer disease are under evaluation for brain injuries. The goal of this study was to conduct a head-to-head in vitro evaluation of 5 tau PET radiotracers in subjects pathologically diagnosed with CTE. Methods: Autoradiography was used to assess the specific binding and distribution of 3 H-flortaucipir (also known as Tauvid, AV-1451, and T807), 3 H-MK-6240 (also known as florquinitau), 3 H-PI-2620, 3 H-APN-1607 (also known as PM-PBB3 and florzolotau), and 3 H-CBD-2115 (also known as 3 H-OXD-2115) in fresh-frozen human postmortem CTE brain tissue (stages I-IV). Immunohistochemistry was performed for phospho-tau with AT8, 3R tau with RD3, 4R tau with RD4 and amyloid-b with 6F/3D antibodies. Tau target density (maximum specific binding) was quantified by saturation analysis with 3 H-flortaucipir in tissue sections. Results: 3 H-flortaucipir demonstrated a positive signal in all CTE cases examined, with varying degrees of specific binding (68.7% 6 10.5%; n 5 12) defined by homologous blockade and to a lesser extent by heterologous blockade with MK-6240 (27.3% 6 13.6%; n 5 12). The 3 H-flortaucipir signal was also displaced by the monoamine oxidase (MAO)-A inhibitor clorgyline (43.9% 6 4.6%; n 5 3), indicating off-target binding to MAO-A. 3 H-APN-1607 was moderately displaced in homologous blocking studies and was not displaced by 3 H-flortaucipir; however, substantial displacement was observed when blocking with the b-amyloid-targeting compound NAV-4694. 3 H-MK-6240 and 3 H-PI-2620 had negligible binding in all but 2 CTE IV cases, and binding may be attributed to pathology severity or mixed Alzheimer disease/CTE pathology. 3 H-CBD-2115 showed moderate binding, displaced under homologous blockade, and aligned with 4R-tau immunostaining. Conclusion: In human CTE tissues, 3 H-flortaucipir and 3 H-APN-1607 revealed off-target binding to MAO-A and amyloid-b, respectively, and should be considered if these radiotracers are used in PET imaging studies of patients with brain injuries. 3 H-MK-6240 and 3 H-PI-2620 bind to CTE tau in severe-or mixed-pathology cases, and their respective 18 F PET radiotracers warrant further evaluation in patients with severe suspected CTE.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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 teacher head, 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".