P3–091: [18F]NAV4694 shows higher binding and wider dynamic range compared with [11C]PiB in Alzheimer's disease postmortem tissue
Bibliographic record
Abstract
[18 F]amyloid imaging agents have low dynamic range when compared with [11 C]PIB, the benchmark PET agent for quantifying brain amyloidosis. In this context, the new amyloid imaging agent [18 F]NAV4694 has been considered a promising amyloid agent. Here, we compare the binding and dynamic range of [11 C]PIB and [18 F]NAV4694 in AD post-mortem brains by means of in vitro autoradiography. Since [18 F]NAV4694 affinity (Kd = 2.4 nM) is higher than [11 C]PIB (Kd = 4.5 nM), we predict a higher binding of [18 F]NAV4694 in post-mortem AD brains. Controls (CN; age=74.6 ± 11.7; n=25) and AD (age=75.3 ± 8.6; n=13) human samples (Post-mortem delay: CN=20.79 ± 14.51; AD=23.85 ± 21.63) containing the prefrontal cortex (PFC), hippocampus (HIP), posterior cingulate cortex (PCC), inferior parietal cortex (IPC) and striatum (ST) were acquired from the Douglas Hospital Brain Bank/Canada. Slices were classified according to the CERAD criteria. For autoradiography, we incubated frozen slices (20 μm thick) during 2 hours using [18 F] NAV4694 (specific activity 60 Ci/mmol) and [11 C]PIB (302 Ci/mmol). The imaging plates were scanned using BAS5000 (Fuji-Film). The image outcome measure was the total binding obtained in the same tissue region. [11 C]PIB showed increased binding in AD brains compared to CN brains [PFC (p=0.0001); PCC(p=0.0037); and IPC (p=0.0001)]. However, it failed to detect amyloid plaques in the hippocampus (p=0.0798). [18 F]NAV4694 was capable to differentiate CN from AD in all brain regions studied (PFC, p=0.0001; HIP, p=0.0001; PCC, p=0.0001; and IPC, p=0.0001). No difference was found in ST. Dynamic range was higher for [18 F]NAV4694 than [11 C]PIB (11.10 vs. 8.2 z-scores; p=0.04). Assuming z-score of 2 as cutoff value, chi-square showed high confidence between observed and expected to [18 F]NAV4694 (χ 2 =2.654; p=0.9151) but significantly discrepancy to [11 C]PIB (χ 2 =21.477; p=0.003).
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".