IC‐P‐004: PET imaging of Alzheimer's transgenic mice at an early age with F‐18 quinoline
Bibliographic record
Abstract
Amyloid deposits are intimately associated with elevated levels of transition metals (Zn, Cu). Previously we reported the synthesis and preliminary evaluation of F-18 labeled quinoline (HOQ), a weak metal chelator. Here we report the evaluation of this agent in imaging amyloid plaques in double transgenic (Tg) AD mice of varying ages (6-15 mo). F-18 HOQ was prepared as previously reported by us. Transgenic mice (n=3-4 per group), (ages: 6, 12 and 15 mo) with double mutation (APP/PS1) for AD were used. PET/CT (Siemens Inveon®) scan was obtained immediately after injection of F-18 HOQ (40-100 micro Ci) and imaging continued for 20 min. In a separate study, a control (WT) and 2 AD mice were sacrificed after 5 min of injection, and ex-vivo images were obtained. Tissue sections were stained with specific (Abeta-42) antibody. Tg mice brains had slower washout of the tracer compared to controls. ROI analysis showed that cortex to cerebellum ratios were close to 1 in control mice and increased with age in Tg mice. Tg mice at 6 mo, had increased (1.5 times vs. cerebellum) but diffuse uptake in the cortex whereas older mice had discrete and higher (>2.5 for 12 mo and >3.5 for 15 mo) uptake at 5 min post injection. Ex-vivo images of AD mice had enhanced tracer uptake in cortex, hippocampus and olfactory bulbs compared to cerebellum and there were no differences in control mouse. Tracer uptake measured by PET imaging correlated with amyloid burden by immuno-histopathology. Plaque deposition in olfactory bulbs visualized in Tg mice but not in control mice. Regional brain uptake and kinetics of the tracer in mice may be analyzed, similar to image analysis in larger animals. PET imaging with F-18 quinolines may be used to follow the progression of the Alzheimer's disease in different mice models. This would be a valuable tool in assessing the therapeutic efficacy and assist in accelerating the AD drug development process. These data warrant further evaluation of F-18 quinolines in early diagnosis of AD.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".