Radiosynthesis of a Bruton's tyrosine kinase inhibitor, [<sup>11</sup>C]Tolebrutinib, via palladium‐NiXantphos‐mediated carbonylation
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Bruton's tyrosine kinase (BTK) is a key component in the B‐cell receptor signaling pathway and is consequently a target for in vivo imaging of B‐cell malignancies as well as in multiple sclerosis (MS) with positron emission tomography (PET). A recent Phase 2b study with Sanofi's BTK inhibitor, Tolebrutinib (also known as [a.k.a.] SAR442168, PRN2246, or BTK'168) showed significantly reduced disease activity associated with MS. Herein, we report the radiosynthesis of [ 11 C]Tolebrutinib ([ 11 C] 5 ) as a potential PET imaging agent for BTK. The N ‐[ 11 C]acrylamide moiety of [ 11 C] 5 was labeled by 11 C‐carbonylation starting from [ 11 C]CO, iodoethylene, and the secondary amine precursor via a novel palladium‐NiXantphos ‐ mediated carbonylation protocol, and the synthesis was fully automated using a commercial carbon‐11 synthesis platform (TracerMaker™, Scansys Laboratorieteknik). [ 11 C] 5 was obtained in a decay‐corrected radiochemical yield of 37 ± 2% ( n = 5, relative to starting [ 11 C]CO activity) in >99% radiochemical purity, with an average molar activity of 45 GBq/μmol (1200 mCi/μmol). We envision that this methodology will be generally applicable for the syntheses of labeled N ‐acrylamides.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it