Quantification of [ <sup>11</sup> C]ABP688 binding in human brain using cerebellum as reference region: biological interpretation and limitations
Bibliographic record
Abstract
Abstract In vitro data from primates provide conflicting evidence about the cerebellum’s suitability as a reference region for quantifying type 5 metabotropic glutamate receptor (mGluR5) binding parameters with positron emission tomography (PET). To address this, we first measured mGluR5 density in postmortem human cerebellum using [ 3 H]ABP688 autoradiography (n=5) and immunohistochemistry (n=6). Next, in vivo experiments were conducted in healthy volunteers (n=6) using a high-resolution PET scanner (HRRT) to compare [ 11 C]ABP688 binding potential (BP ND ) values obtained with reference tissue methods and the two-tissue compartment model vs. metabolite-corrected arterial input function. The postmortem data showed that, relative to the hippocampus, the cerebellum had 26% less mGluR5 immunoreactivity and 94% fewer [ 3 H]ABP688 binding sites. In vivo brain regional [ 11 C]ABP688 BP ND values using the cerebellum as a reference region were highly correlated with BP ND values and distribution volumes derived by arterial input methods (R 2 > 0.9). The absence of cerebellar allosteric binding sites might reflect the presence of distinct mGluR5 isoforms or conformational state. Together with our PET data, these results support the proposition that [ 11 C]ABP688 BP ND using cerebellum as a reference region provides accurate quantification of mGluR5 allosteric binding in vivo .
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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 | 0.009 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".