Promising Performance of 4HMS, a New Zirconium-89 Octadendate Chelator
Bibliographic record
Abstract
Abstract Over the last decade, the interest in zirconium-89 (89Zr) as a positron-emitting radionuclide increased considerably because of its standardized production and its physical half-life (78.41 h), which matches the biological half-life of antibodies and its successful use in preclinical and clinical applications. So far, desferrioxamine (DFO), a commercially available chelator, has been mainly used as a bifunctional chelating system. However, there are some concerns regarding the in vivo stability of the [89Zr]Zr-DFO complex. In this study, we report the synthesis of an acyclic N-hydroxy-N-methyl succinamide-based chelator (4HMS) with 8 coordination sites and our first investigations into the use of this new chelator for 89Zr complexation. In vitro and in vivo comparative studies with [89Zr]Zr-4HMS and [89Zr]Zr-DFO are presented. The 4HMS chelator was synthesized in four steps starting with an excellent overall yield. Both chelators were quantitatively labeled with 89Zr within 5–10 min at pH 7 and room temperature; the molar activity of [89Zr]Zr-4HMS exceeded (>3 times) that of [89Zr]Zr-DFO. [89Zr]Zr-4HMS remained stable against transmetalation and transchelation and cleared from most tissues within 24 h. The kidney, liver, bone, and spleen uptakes were significantly low for this 89Zr-complex. Positron emission tomography images were in accordance with the results of the biodistribution in healthy mice. Based on DFT calculations, a rationale is provided for the high stability of 89Zr-4HMS. This makes 4HMS a promising chelator for future development of 89Zr-radiopharmaceuticals.
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.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".