Thorium chelators for targeted alpha therapy: Rapid chelation of thorium‐226
Why this work is in the frame
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Bibliographic record
Abstract
One of the main challenges in targeted alpha therapy is assuring delivery of the α‐particle dose to the targeted cells. Thus, it is critical to identify ligands for α‐emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium‐227 ( t 1/2 = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed‐phased HPLC and gamma spectroscopy. Studies revealed that high 227 Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me‐3,2‐HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H 4 octapa 3 (65%) and H 4 py4pa 6 (87%). No reaction occurred with H 4 neunpa‐ p ‐Bn‐NO 2 4 , and the chelation reaction with another pa ligand H 4 pypa 5 gave inconsistent yields with a very broad radio‐HPLC peak. The ligands spermine‐(Me‐3,2‐HOPO) 4 1 , H 4 octapa 3 , and H 4 py4pa 6 had high stability (i.e., 87% of 227 Th still bound to the ligand) in phosphate‐buffered saline at room temperature over a 6‐day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium‐226 ( t 1/2 = 30.57 min) when heated to 80°C for 5 min.
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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) | 0.001 | 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 | 0.001 |
| 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