A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals
Open accessAbstract
Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated. Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%. Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.
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Fr-221, with its short half-life of 4.9 min, is nearly in radioactive equilibrium after 60-120 min.
“Fr-221, with its short half-life of 4.9 min, is nearly in radioactive equilibrium after 60–120 min (123).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [123]
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- Authors
- Kelly, J. M., Amor-Coarasa, A., Sweeney, E., Wilson, J. J., Causey, P. W., & Babich, J.
- Affiliations
- Weill Cornell Medicine (US)
- Yeshiva University Albert Einstein College of Medicine
- Citigroup (US)
- Canadian Nuclear Laboratories (CA)
- Corresponding author
- Wilson, Justin J.
- Published
- 2021-04-21
- OpenAlex
- W4236969947
- Cited by
- 11
- References
- 31
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 7
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- Research Square (acceptedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Physical Sciences › Physics and Astronomy › Radiation › Radioactive Decay and Measurement Techniques
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
- Keywords
- actinium-225, radiopharmaceutical quality control, radiochemical purity, secular equilibrium, targeted alpha therapy, radiolabeling
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