Preparation of an astatine-211 aqueous solution by dry distillation and dissolution in pure water

Objectives: Astatine-211 (²¹¹At) is a promising radionuclide for targeted alpha therapy of metastatic cancers. The production of ²¹¹At is accomplished in the ²⁰⁹Bi(α, 2n)²¹¹At nuclear reaction using an accelerator. Typically, ²¹¹At is isolated from the irradiated Bi target through a dry distillation method and dissolved in various solutions. In many cases, methanol or chloroform is used as solvent for dry distilled ²¹¹At. However, these solutions are toxic to living body, and it is desirable to dissolve dry distilled ²¹¹At with non-toxic aqueous solution for clinical use of ²¹¹At. Our group have been preparing the clinical trial of [²¹¹At]-sodium astatide ([²¹¹At]NaAt) as a reagent for targeted alpha therapy of thyroid cancer. This reagent is prepared by adding aqueous ascorbic acid solution to dry distilled ²¹¹At dissolved in pure water. Here, we report our recent results of preparation method for dry distilled ²¹¹At dissolved in pure water.

Methods: The ²¹¹At produced in the ²⁰⁹Bi(α, 2n)²¹¹At reaction was supplied from RIKEN through Supply Platform of Short-lived Radioisotopes. The produced ²¹¹At was separated from the irradiated Bi target using the dry distillation apparatus shown in Fig. 1. The irradiated Bi target was put in a quartz column and heated up to 850°C using an electric tubular furnace. The evaporated ²¹¹At was transported to Teflon trap tube, which is cooled by ice water, with mixed N₂ and O₂ gas flow including trace moisture added by a moisture generator. The trapped ²¹¹At was then dissolved in 100 μL of pure water. The separation yield of ²¹¹At was calculated from the ²¹¹At radioactivity in the eluted pure water divided by that in the irradiated Bi target measured with a Ge detector.

Results: Approximately 80% of ²¹¹At (after decay correction) was trapped in the Teflon trap tube. However, the separation yield of ²¹¹At dissolved in 100 μL of pure water fluctuated from 35% to 70%; most of ²¹¹At remained in the Teflon trap tube when the separation yield was low. The remained ²¹¹At in the trap tube was recovered by 2-6 times repeated dissolution with 100 μL of pure water resulting in total separation yield of 65% to 80%. A rough correlation was observed between the separation yield of ²¹¹At and the amount of moisture in the carrier gas during heating of the Bi target, indicating that the proportion of chemical species of ²¹¹At which can be easily dissolved in pure water might be affected by the amount of moisture in the carrier gas. Optimization of separation condition would lead to preparation of ²¹¹At dissolved in small volume of pure water.

Conclusions: It is expected that, by optimization of separation condition, our preparation method for dry distilled ²¹¹At dissolved in pure water would be applied to clinical application of [²¹¹At]NaAt for targeted alpha therapy of thyroid cancer.

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