High Separation Factor, High Molar Activity, and Inexpensive Purification Method for the Production of Pure <sup>165</sup>Er
Bibliographic record
Abstract
Introduction: Auger electron-emitting radionuclides with low (0.001–1 keV) energy, short-range (2–500 nm), and high linear energy transfer (4–26 keV/μm) can play an important role in the targeted radionuclide therapy (TRT) of cancer. 165 Er is a pure Auger electron-emitting radionuclide, making it a useful tool for the fundamental studies of the biological effects of Auger electrons. This work develops a simple, inexpensive, high separation factor, and high molar activity radiochemical isolation process for the production of 165 Er ( t 1/2 10.36 h) suitable for TRT in vitro and in vivo studies using irradiated nat Ho solid targets. Methods: Small medical cyclotron proton-irradiation of nat Ho targets produced 165 Er in GBq scale quantities. 165 Er was isolated using cation exchange chromatographic resin (AG 50W-X8, 200–400 mesh, 20 mL, under atmospheric pressure) using α-hydroxyisobutyric acid (70 mM, pH 4.75) followed by extraction using TK212, TK211, and TK221 extraction chromatographic columns. Radio nuclidic and chemical purity of the final 165 Er were confirmed using HPGe Gamma spectrometry and induction coupled plasma–mass spectrometry analysis, respectively. The purified 165 Er was radiolabeled with two radiometal chelators (DOTA and Crown) and used to produce a new Auger electron-emitting radiopharmaceutical, [ 165 Er]Er-Crown-TATE. Results: Irradiation of 200 mg nat Ho targets with 20–30 μA of 12.8 MeV protons produced 165 Er at 25 ± 5 MBq·μA –1 ·h –1 . The 4.5 ± 0.5 h radiochemical isolation yielded GBq scale of 165 Er in 0.05 M HCl (2 mL) with a radiochemical yield of 78.0 ± 5.6% decay corrected to the end of bombardment (EoB) and a Ho/ 165 Er separation factor of (1.14 ± 0.25) × 10 6 . The product showed high radio nuclidic purity and chemical purity. Concentration-dependent radiolabeling experiments with Crown and DOTA were performed resulting in the successful labeling of 165 Er with high (>90%) radiochemical yield. Radiolabeling experiments with Crown-TATE were performed 8 h after EoB and synthesized [ 165 Er]Er-Crown-TATE at molar activities of 202.4 MBq·nmol –1 at the end of synthesis (EoS). Conclusions: A 3 h cyclotron irradiation and 4.5 h radiochemical separation produced GBq-scale 165 Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutic effects of Auger electron emissions. This will enable future fundamental radiation biology experiments of pure Auger electron-emitting therapeutic radiopharmaceuticals, such as [ 165 Er]Er-Crown-TATE, which will be used to understand the impact of Auger electrons in TRT.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 0.002 |
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".