PET imaging of fructose metabolism in a rodent model of neuroinflammation with 6-[ 18F]fluoro-6-deoxy-D-fructose
Bibliographic record
Abstract
Abstract Introduction:Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[18F]FDF) was developed for PET imaging of fructose metabolism in breast cancer via the fructose-preferred facilitative hexose transporter, GLUT5. In the brain, GLUT5 is predominantly expressed on microglial cells that are activated in response to inflammatory stimuli. We hypothesize that 6-[18F]FDF will specifically image microglia following neuroinflammatory insult.Methods:6-[18F]FDF was evaluated in a neuroinflammation model induced by unilateral injection of lipopolysaccharide (LPS) into the right striatum (50 µg/animal) in male and female rats. Comparison of 6-[18F]FDF and the glucose derivative [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), was performed by longitudinal dynamic PET imaging in vivo. Immunohistochemistry was conducted to examine the presence of activated microglia (Iba-1) and astrocytes (GFAP) in fixed brain tissues.Results:In LPS-injected rats, increased accumulation of radioactivity from 6-[18F]FDF was observed in the ipsilateral striatum compared to the contralateral side at 24-48 hr post-LPS injection, with plateaued uptake at 60-120 min significantly higher in the right (0.985 ± 0.047 SUV) vs. left (0.819 ± 0.033 SUV) striatum at 48 h (P= 0.002; n = 4M/3F). The ipsilateral-contralateral difference in striatal 6-[18F]FDF uptake expressed as binding potential peaked at 48 h (male: 0.25 ± 0.03; female: 0.11 ± 0.03) and was significantly decreased at later time points of one, two and four weeks; and was higher in male rats (P= 0.017). In contrast, increased [18F]FDG uptake was observed in the ipsilateral striatum compared to the contralateral striatum and was highest at one week post-LPS injection. Iba-1 and GFAP immunohistochemistry confirmed LPS-induced activation of microglia and astrocytes in the ipsilateral striatum.Conclusions:This proof-of-concept study revealed an early response of 6-[18F]FDF to neuroinflammatory stimuli in rat brain. 6-[18F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in the brain with applications in neuroinflammatory and 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| 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".