IC‐P‐136: SYNTHESIS AND <i>IN VIVO</i> BRAIN PET EVALUATION OF 1‐METHYL‐4‐PIPERIDYL <i>P‐</i><sup>18</sup>[F]FLOUROBENZOATE (TRV6501): A BUTYRYLCHOLINESTERASE‐SPECIFIC RADIOLIGAND FOR ALZHEIMER'S DISEASE
Bibliographic record
Abstract
There are currently no effective means to definitively diagnose Alzheimer's disease (AD) during life. Molecular imaging of amyloid or tau pathology in the AD brain is limited because similar changes are found in brains of ∼30% of cognitively normal individuals. We have recently shown that the protein butyrylcholinesterase (BChE), typically present in high levels in the AD cerebral cortex, is a highly sensitive and specific biomarker for the disease and could therefore provide enhanced accuracy as an AD diagnostic. We have developed a class of radiotracers for brain imaging that target BChE. The synthesis and in vivo evaluation of one such positron emission tomography (PET) BChE radiotracer, 1-methyl-4-piperidyl p-[F]flourobenzoate (TRV6501), is described here. 1-methyl-4-piperidyl p-[F]flourobenzoate (TRV6501) was synthesized and injected into 5XFAD mice (n=3) and WT/BCHE-KO counterparts (n=3) for dynamic PET evaluation over 60min. Retention of TRV6501 was assessed. Cerebral uptake of TRV6501 indicated that this radiotracer crossed the blood-brain barrier. Significant retention was observed in BChE-rich regions of the 5XFAD brain including the cerebral cortex and amygdala and basal ganglia. In WT/BChE-KO there was considerably less retention of TRV6501 localized mainly to white matter regions. These preliminary findings suggest target engagement by TRV6501 (a BChE-specific radioligand) with BChE-associated pathology in the 5XFAD brain. Further dynamic PET quantification and kinetic modelling will provide a rigorous in vivo validation of TRV6501 as an AD diagnostic. If successful, this brain imaging method may enhance the accuracy and timely detection of Alzheimer's disease in humans.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".