Improving the Availability of the Therapeutic Radionuclide Astatine-211

Investigators at the University of Washington have developed methods that consistently provide high production and recovery yields of astatine-211.

Image courtesy of Donald Hamilin, University of Washington
Research scientist conducting the “wet chemisty” astatine-211 isolation procedure within a charcoal-filtered glovebox. All steps of the isolation procedure are conducted within the glovebox. Because of the lack of high-energy gamma or beta rays, large quantities (130+ mCi) of astatine-211 can be worked with in a glovebox. Chemical steps for isolation of astatine-211 are described in detail in Applied Sciences 3, 636 (2013).

The Science

The alpha-emitting radionuclide astatine-211 holds great potential for treatment of cancer through development of targeted molecular radiotherapy agents.  However, the availability of astatine-211 to conduct preclinical and clinical investigations for its use in cancer therapy has been severely limited due to the fact it is not found in nature, its half-life is short (7.12 hours), and its chemistry is not well understood.  Researchers have developed improved methods for production of man-made astatine-211, which will help to make it more available for scientific investigations.

The Impact

The DOE Isotope Program is taking the approach to making astatine-211 more available by scaling-up its production on cyclotrons that produce the requisite alpha beams, so that it can be made and shipped to interested investigators within regions of the U.S.  At the University of Washington, scale-up of the bismuth irradiation was accomplished by increasing the alpha beam area and intensity on the bismuth target, however, attempts to scale-up the recovery of astatine by the normal “dry distillation” approach proved to be difficult due to inconsistencies in isolated yields.  To circumvent this problem, an alternative isolation approach was developed to improve the consistency of astatine-211 recovered yields.

Summary

Scale-up of astatine-211 production required redesign and building of a new target system on the clinical cyclotron at the University of Washington, which is in the process of joining the suite of isotope production facilities under the umbrella of the DOE Isotope Program. Because the bismuth metal used as a target is low melting (272°C) its irradiated surface area was increased to provide adequate cooling during high beam intensity irradiations. This increase in target size made it difficult to fit into commercially available tube ovens for isolation of astatine-211 by distillation, and the larger surface area of the glassware used decreased the recovered yields. An alternative isolation approach termed “wet chemistry” was developed to improve the process. In that approach the astatine-211 was separated from the target by dissolving the bismuth in acid, followed by extracting it into another solvent that excluded bismuth. After washing steps to remove all bismuth, astatine-211 was isolated by back-extraction into aqueous base. This procedure provided high and consistent (78 ± 11%) isolated yields in 55 production runs.

Contact

Professor D. Scott Wilbur
University of Washington
dswilbur@uw.edu
(206) 616-9246

Funding

Department of Energy, Office of Science, Nuclear Physics, Isotope R&D Grant #DE-SC0004046.

Partial support for the Postdoctoral Fellow, Dr. Katherine Gagnon, was provided by the National Research Council of Canada.

Publications

Gagnon K., Risler R., Pal S., Hamlin D., Orzechowski J., Pavan R., Zeisler S., and Wilbur D.S., Design and evaluation of an external high-current target for production of 211At. J. Labelled Compounds and Radiopharmaceuticals 55, 436 (2012).

Wilbur D.S.  Enigmatic Astatine. Nature Chemistry 5, 246, (2013).

Balkin E.R., Hamlin D.K., Gagnon K., Chyan M.-K., Pal S., Watanabe S. and Wilbur D.S., Evaluation of a Wet Chemistry Method for Isolation of Cyclotron Produced [211At]Astatine. Applied Sciences 3, 636 (2013).