ArticleEJNMMI radiopharmacy and chemistry2025
Ac-225 radiochemistry through the lens of [
Article in EJNMMI radiopharmacy and chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- [International journal of molecular sciences · 2026Article
- Inline gamma spectroscopy and liquid scintillation HPLC reveal daughters inEJNMMI radiopharmacy and chemistry · 2026Article
- FOLR1-targeted actinium-225-based alpha-particle therapy eliminates ovarian cancer.Science advances · 2026Article
- High-energy resolution X-ray spectroscopy reveals bonding characteristics of LaCommunications chemistry · 2026Article
- Alpha Therapy Beyond TOC and TATE-Production, Quality Control, and In-Human Results for the SSTR2 Antagonist DOTA-LM3.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Quality control of actinium-225 andEJNMMI radiopharmacy and chemistry · 2026Article
- Emergence of a barium metal-organic framework for mitigating off-target effects of alpha radionuclide therapy.Theranostics · 2026Article
- Prostate Cancer Imaging Beyond PSMA: Applications of GRPR, AR, and Amino Acid Tracers.Diagnostics (Basel, Switzerland) · 2025Review
- Highlight selection of radiochemistry and radiopharmacy developments by editorial board.EJNMMI radiopharmacy and chemistry · 2025Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeted alpha therapy with Ac-225 showed to be effective in treating metastatic cancers. However, the complex decay chain requires optimized radiolabeling and quality control. This study aims to determine critical parameters and establish optimal labeling and accurate measuring techniques for radiochemical yield and purity with DOTA-TATE as a model molecule. Ac-225 sources were analyzed for metals (ΣFe, Zn, Cu) and quantified by UPLC. Optimization of radiolabeling kinetics for clinical conditions was performed in regards to temperature (20-90 °C), heating time (5-60 min), pH (2.5-10, with/without excess of metal ions), buffers, quenchers, volume (0.1-10 mL) and molar activity (90-540 kBq/nmol). The quality control was investigated using radio-TLC/HPLC by changing gradient to evaluate peak separation, radiolysed peptide and impurity separation.
resultsMetal ingrowth was observed in Ac-225 stocks (n = 3), (time of arrival: 17.9, 36.8 and 101.4 nmol per 10 MBq). Optimal radiochemical yields were achieved with > 80 °C (20 min) at pH 8.5 (15 mM TRIS) up to 270 kBq. Labeling at a high pH showed a higher RCY, even in presence of an excess of metals. High stability (RCP > 90%) was achieved after addition of quenchers (cysteine, methionine, ascorbate, histidine, or gentisic acid (35 mM)) up to 24 h. For optimal determination of the radiochemical purity (indirect HPLC) fifty fractions are required.
conclusionThe quality of Ac-225 labeled DOTA-radiopharmaceuticals is highly dependent on the pH and stabilization (buffer/quencher). Within this research it is demonstrated that optimized quality control methods and accurate measurement of the radiolabeling kinetics are crucial to ensure safe implementation for patient treatment.
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