Development and Preclinical Evaluation of PET Radiotracers Targeting Adenosine A<sub>1</sub> Receptors
Bibliographic record
Abstract
Several adenosine A 1 receptor (A 1 R) radiotracers for positron emission tomography (PET) have been developed to study their neuromodulatory functions and role in brain disorders. While two xanthine-based radiotracers ([ 11 C]MPDX and [ 18 F]CPFPX) have been used in humans, we aimed to improve the metabolic stability and specific binding. Guided by structure–activity relationship (SAR) studies, 10 derivatives were synthesized with binding affinities up to 0.12 nM. Three subnanomolar candidates ( 3, 8, 9 ) were radiolabeled with C-11 ( t 1/2 = 20.4 min) for evaluation using in vivo PET imaging and ex vivo rodent brain biodistribution. Although [ 11 C] 8 demonstrated a higher blood–brain barrier (BBB) permeability, negligible in vivo specific binding was observed. Ex vivo studies indicated that all three compounds are substrates for brain efflux pumps. Despite optimized affinity, BBB permeability and in vivo binding specificity remain challenges. These findings inform development of nonxanthine A 1 R radiotracers and highly potent CNS A 1 R drugs.
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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 | 0.000 |
| 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 | 0.000 | 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".