Autoradiographic comparison between [11C]PiB and [18F]AZD4694 in human brain tissue
Bibliographic record
Abstract
Abstract Background Amyloid-β imaging through positron emission tomography (PET) has significantly transformed Alzheimer’s disease (AD) research. [11C]PiB has been widely used for imaging β-amyloid plaques due to its high affinity and selectivity for amyloid deposits. [18F]AZD4694 is a more recently developed amyloid-PET imaging agent, which structurally resembles PiB and has less non-specific binding in the white matter than other 18F-labeled compounds. The purpose of this study is to compare the in vitro binding properties of the amyloid-PET radiotracers [11C]PiB and [18F]AZD4694 in post-mortem human brain tissue. Total binding was assessed by autoradiography in prefrontal, inferior parietal, posterior cingulate cortices and hippocampal sections of healthy control (HC) and AD autopsy-confirmed brain tissues. Furthermore, the displacement of [18F]AZD4694 by unlabeled PiB was evaluated in the above-mentioned sections of AD brain tissues. Results For both radiotracers, we found significant differences (p < 0.0001) between HC and AD tissues binding in the prefrontal cortex ([11C]PiB Cohen’s d = 3.424, [18F]AZD4694 Cohen’s d = 5.070), inferior parietal cortex ([11C]PiB Cohen’s d = 3.156, [18F]AZD4694 Cohen’s d = 3.959), posterior cingulate cortex ([11C]PiB Cohen’s d = 1.781, [18F]AZD4694 Cohen’s d = 3.434), and hippocampus ([11C]PiB Cohen’s d = 1.320, [18F]AZD4694 Cohen’s d = 3.696). Higher binding was detected for [18F]AZD4694 compared to [11C]PiB in AD prefrontal, inferior parietal and posterior cingulate cortices, while binding in the hippocampus was comparable for both radioligands. Strong correlations between [18]AZD4694 and [11C]PiB were found in the prefrontal (R = 0.959, p < 0.0001), inferior parietal (R = 0.893, p < 0.0001), posterior cingulate (R = 0.838, p = 0.0006) cortices and hippocampus (R = 0.750, p < 0.0001). Bland–Altman analyses revealed strong agreement between [11C]PiB and [18F]AZD4694 in the prefrontal, inferior parietal, and posterior cingulate cortices, but lower agreement in the hippocampus. Displacement studies confirmed high binding affinity of PiB in all tissues, indicating that both amyloid-PET agents compete for the same binding sites. Conclusions This head-to-head study provides evidence that while [18F]AZD4694 and [11C]PiB bindings are highly correlated with both tracers competing for the same binding sites, [18F]AZD4694 has a slightly higher effect size when comparing between neuropathologically-confirmed AD and HC brain tissues.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
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".