Evaluation of the novel <sup>18</sup>F‐labeled PET tracer SMBT‐1 for imaging astrogliosis in healthy elderly controls and A+/T+/(N+) Alzheimer's disease patients
Bibliographic record
Abstract
Abstract Background Neuroinflammatory changes, characterized by reactive astrocytes and activated microglia, contribute greatly to neurodegeneration throughout the course of Alzheimer’s diseases (AD). Reactive astrocytes overexpress monoamine oxidase‐B (MAO‐B) in the outer mitochondrial membrane. For imaging astrogliosis in the human brain, we developed the novel MAO‐B PET tracer named 18F‐SMBT‐1. We aimed to investigate the binding properties of 18F‐SMBT‐1 in healthy elderly controls and AD patients. Methods After in silico preclinical evaluation were performed for the assessment of binding affinity and selectivity of 18F‐SMBT‐1, 9 participants, 5 healthy elderly controls (3F/2M, 78.5±6.0 yrs, 3 A‐/T‐/(N‐) and 2 A+/T‐/(N‐)) and 4 A+/T+/(N+) AD patients (3F/1M, 76.8±1.4 yrs), underwent 18F‐SMBT‐1 PET, amyloid PET with 18F‐NAV4694, tau PET with either 18F‐MK6240 (n=7) or 18F‐PI2620 (n=2), and 3D‐MPRAGE MRI. While Ab burden was expressed in Centiloids, tau tissue ratios were generated using the cerebellar cortex as reference region. 18F‐SMBT‐1 studies were expressed as SUV or as tissue ratios using the cerebellar white matter as reference region. To ascertain 18F‐SMBT‐1 selective binding to MAO‐B, participants underwent a second 18F‐SMBT‐1 scan after receiving 5mg selegiline twice daily for 5 days. Results SMBT‐1 showed strong and reversible binding to MAO‐B, and low binding affinity to other enzymes, receptors and misfolded proteins such as amyloid‐β and tau.18F‐SMBT‐1 yielded high contrast images at 60‐90 min post injection, with high tracer retention in basal ganglia, intermediate in neocortical regions, and lowest in cerebellum which tightly follows the known regional brain distribution of MAO‐B (R2=0.82). In AD patients, 18F‐SMBT‐1 retention was significantly higher in parahippocampus, fusiform and inferior temporal gyrus. More than 85% of 18F‐SMBT‐1 signal was blocked and no residual cortical activity was observed after the selegiline regimen, indicating high selectivity for MAO‐B. Conclusions 18F‐SMBT‐1 is the highly selective MAO‐B tracer, which will enable the assessment of astrogliosis in the human brain. The confirmation of these preliminary findings with 18F‐SMBT‐1 will require examination of a much larger series, including participants with MCI and prodromal 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 | 0.001 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".