New Elegant Method for Rapid Recovery of Anti-Cancer Agent At-211

A high-speed, high-yield recovery approach for At-211 means improved availability of this cancer-treating isotope.

Image courtesy of Jon Burns, Texas A&M University
At-211 – ketone interaction within the chromatography column.

The Science

Astatine is an extremely rare element. It occurs naturally only due to the radioactive decay of other elements in the earth’s crust. There are no known stable isotopes of astatine, and none of its isotopes has a half-life greater than 8 hours. This means half of the nuclei in a sample of astatine will decay every eight hours. One isotope of the element, At-211, has shown promise in cancer treatment. However, because of its short half-life, scientists need a rapid system with high yield to recover the At-211 for medical use. In this research, scientists developed a purification system based on a newly discovered chemical interaction of At-211 with a class of chemicals known as ketones. This system results in a high purity, high yield recovery of At-211 in roughly 10 to 20 minutes.

The Impact

Researchers are increasingly interested in targeted alpha therapy (TAT) drugs for cancer treatment. TAT is a process that uses an atom that releases alpha radiation capable of causing large amounts of damage at a short range. This atom is attached to a molecule targeted at cancer cells. At-211 is of particular interest for TAT because it emits one alpha particle and has a moderately-short half-life of 7.2 hours. These characteristics help doctors control damage to the patient’s body. Although At-211 is not widely available, researchers have used the isotope in a number of clinical trials. The trials include treatment of malignant brain tumors, ovarian cancer, and a current study treating advanced blood and lymph system cancers. The new purification method results in high yields of At-211 faster than previous methods.

Summary

Making At-211 requires a nuclear reaction resulting from bombarding a metal plate of bismuth with alpha particles using a particle accelerator such as the Texas A&M K150 cyclotron. The At-211 is trapped in the bismuth target and must be extracted through a chemical process. Of the two approaches generally used to recover the At-211, completely dissolving the target followed by chemical processing results in a more consistent At-211 yield. Researchers have found that using ketone solvents in the wet chemical process improves the overall amount of At-211 purified.

The biggest challenge of recovering purified At-211 is the amount of time it takes and the need for sophisticated equipment that runs continuously. To overcome this challenge, scientists explored the use of chromatography to extract At-211. Chromatography is a process of breaking down a solution into its various parts in a single step. Using this method reduces the time and resources necessary to extract At-211. The extraction chromatography system used in this project is based on a chemical called 3-octanone. The results indicate that this process produces high-quality At-211 in about 10 to 20 minutes using minimal resources and mild chemicals, which should be compatible with human use. This streamlined process can improve availability of this potentially useful isotope, increasing its availability to the medical research community through the DOE Isotope Program’s National Isotope Development Center.

Contact

Sherry Yennello
Texas A&M University
yennello@tamu.edu

Jon Burns
Texas A&M University
burns.jon@tamu.edu

Funding

This work was supported by Texas A&M University through the Bright Chair in Nuclear Science, by the Department of Energy (DOE), and by the DOE Isotope Program, managed by the Office of Science. Additionally, this work was enabled by the Texas A&M Nuclear Solutions Institute.

Publications

Burns, J. D. et al. Astatine partitioning between nitric acid and conventional solvents: indication of covalency in ketone complexation of AtO +. Chem. Commun. 56, 9004–9007 (2020). [DOI: 10.1039/D0CC03804K]

Burns, J. D. et al. Rapid recovery of At-211 by extraction chromatography. Sep. Purif. Technol. 256, 117794 (2021). [DOI: 10.1016/j.seppur.2020.117794]

Related Links

Researchers work to establish isotope production at Texas A&M University, The National Laboratories Office of the Texas A&M University System News

Researchers report fastest purification of astatine-211 needed for targeted cancer therapy, Texas A&M University Engineering News

From hours to minutes: Process cuts time to purify cancer-therapy isotope, Research @ Texas A&M News

Highlight Categories

Program: NP

Performer: University

Additional: Collaborations , NNSA