Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas
Bibliographic record
Abstract
<ns4:p> <ns4:italic>Purpose</ns4:italic> : In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- <ns4:sup>18</ns4:sup> F-fluoroethoxy)-L-tryptophan ( <ns4:sup>18</ns4:sup> F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. </ns4:p> <ns4:p> <ns4:italic>Procedures:</ns4:italic> Uptake of <ns4:sup>18</ns4:sup> F-L-FEHTP was determined in wild-type C57BL/6 mice by <ns4:italic>ex vivo</ns4:italic> biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. </ns4:p> <ns4:p> <ns4:italic>Results:</ns4:italic> Uptake of <ns4:sup>18</ns4:sup> F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced <ns4:sup>18</ns4:sup> F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in <ns4:sup>18</ns4:sup> F-L-FEHTP uptake in the pancreas, and there was no significant correlation of <ns4:sup>18</ns4:sup> F-L-FEHTP uptake with beta cell mass. </ns4:p> <ns4:p> <ns4:italic>Conclusions:</ns4:italic> <ns4:sup>18</ns4:sup> F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, <ns4:sup>18</ns4:sup> F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes. </ns4:p>
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".