Validation of A Novel MAO‐B PET tracer [<sup>18</sup>F]SMBT‐1 on postmortem human brain samples
Bibliographic record
Abstract
Abstract Background Neuroinflammation in various neurodegenerative conditions involves reactive astrogliosis that overexpresses glial fibrillar acid protein (GFAP) as well as monoamine oxidase‐B (MAO‐B). Recently, we developed a reversible MAO‐B PET tracer, [18F]SMBT‐1. Initial clinical PET studies demonstrated that [18F]SMBT‐1 showed higher regional binding not only amyloid (Aβ)‐positive Alzheimer’s disease (AD) but also Aβ‐negative elderly cognitively normal (CN). To validate initial clinical finding, we investigate the binding of [18F]SMBT‐1 in postmortem human brain samples. Methods In vitro autoradiography of [18F]SMBT‐1 (MAO‐B), [18F]Florbetaben (Aβ), and [3H]MK‐6240 (Tau) was performed using postmortem brain sections from CN and AD. In vitro binding assay of [18F]SMBT‐1 was performed against brain homogenates from CN, argyrophilic grain disease (AGD), Lewy body disease (LBD), and frontotemporal lobar degeneration with TDP‐43 (FTLD‐TDP). GFAP levels were measured to investigate the association with tracer binding. Double immunohistochemistry of MAO‐B and A1/A2 reactive astrocyte markers were performed to understand the relationship of astrocytic phenotype in MAO‐B expressing astrocytes. Results Higher specific binding of [18F]SMBT‐1 was observed in Aβ‐positive/Tau‐positive AD brain sections. Interestingly, intense patchy signal of [18F]SMBT‐1 was observed in Aβ‐positive/Tau‐negative CN brain section, which was partially co‐localized with that of Aβ detected by [18F]Florbetaben. These observations were consistent with the findings of clinical [18F]SMBT‐1 PET study. In the brain samples of AGD, LBD and FTLD‐TDP, the amount of [18F]SMBT‐1 binding was correlated with GFAP levels. Double immunostaining demonstrated that MAO‐B was expressed in both A1 and A2 reactive astrocytes. Conclusions Significant [18F]SMBT‐1 binding was detected in the postmortem brains of both AD and Aβ‐positive/Tau‐negative CN, reflecting reactive astrogliosis induced by early Aβ accumulation. [18F]SMBT‐1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".