P2‐385: Binding and pharmacokinetic properties of novel <sup>18</sup>F‐labeled agents for in vivo imaging of tau pathology in Alzheimer's disease
Bibliographic record
Abstract
The deposition of senile plaques and neurofibrillary tangles represents a pathological hallmark of Alzheimer's disease (AD). Individual evaluation of the distributions of senile plaques and neurofibrillary tangles is desirable to obtain a better understanding of the pathophysiology of AD. However, no surrogate markers exist that allow evaluation of the severity of tau pathology in AD brains. To develop novel PET imaging agents with high binding specificity for neurofibrillary tangles, we evaluated the profiles of novel F-labeled compounds (Cpd.B and C) as candidate tau-imaging probes. Binding selectivity of test compounds for senile plaques and neurofibrillary tangles was evaluated by fluorescence microscopy and autoradiography of postmortem AD brains. Binding affinity of test compounds to PHF-tau was examined by in vitro binding assay. Blood-brain barrier permeability was assessed by intravenous administration of test compounds to mice. Microscopic observation demonstrated that both Cpd.B and C stained neurofibrillary tangles intensely and stained senile plaques faintly in AD brain sections. Autoradiographic study of AD brain sections additionally demonstrated selective binding ability of a tracer dose of F-labeled Cpd.B and C to neurofibrillary tangles. In vitro binding assay indicated the high binding affinity of these compounds to PHF-tau. Furthermore, biodistribution study of [F]Cpd.C in mice exhibited excellent brain uptake (6.0 % injected dose/g at 2 min post injection) and rapid clearance (1.3 % injected dose/g at 2 min post injection) from normal brain tissue. The optimization of the pharmacokinetic properties of these compounds is now in progress. These findings suggest that [F]Cpd.C is a potential candidate as a PET tracer for imaging tau pathology in AD patients.
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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) | 0.000 | 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) | 0.001 | 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".