Synthesis and Evaluation of Fluorinated Peptidomimetics Enabling the Development of <sup>18</sup> F‐Labeled Radioligands Targeting Muscarinic Acetylcholine Receptor Subtype M3
Bibliographic record
Abstract
The muscarinic acetylcholine receptor subtype M3 is validated as a promising target for imaging and therapy in breast cancer. Transcriptomic and proteomic profiling reveal its overexpression, particularly in triple‐negative breast cancer. To overcome challenges in developing selective M3 inhibitors, fluorinated peptidomimetic compounds are designed featuring a β‐alanine‐glycine scaffold that mimics key M3 pharmacophore elements. These constructs show strong potential as lead structures for 18 F‐labeled positron emission tomography (PET) radioligands, as demonstrated with lead compound 24 , exhibiting M3‐selective binding (M1/M3, M2/M3, M4/M3, and M5/M3 > 45) with an IC 50 value of 0.3 μM. Compound [ 18 F]24 is prepared as the first M3‐selective PET radioligand using reductive amination with 4‐[ 18 F]fluorobenzaldehyde, in a 35% decay‐corrected radiochemical yield. Radioligand [ 18 F]24 is tested for PET imaging of M3 receptors in preclinical breast cancer models.
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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 | 0.002 | 0.001 |
| 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".