Towards elucidating the radiochemistry of astatine \u2013 Behavior in chloroform

Emma Aneheim,Sture Lindegren,Christian Ekberg,Per Albertsson,Stig Palm,Holger Jensen

doi:10.1038/s41598-019-52365-5

Abstract

Targeted alpha therapy of disseminated cancer is an emerging technique where astatine-211 is one of the most promising candidate nuclides. Although astatine has been known for over 70 years, its chemistry is still largely unexplored, mainly due to the lack of stable or long-lived isotopes. However, substantial amounts of astatine-211 can be produced in cyclotrons by the bombardment of natural bismuth. The astatine can be recovered from the resulting irradiated target material through either wet extraction or dry-distillation. Chloroform has become an important intermediate solvent for the recovery of astatine after production, especially following dry distillation. In this work, the radiochemistry of astatine in chloroform was investigated using evaporation, solvent extraction, chromatographic methods and molecular modeling. The extraction of astatine in chloroform led to the formation of multiple astatine species, allowing for evaporation of the solvent to dryness without any loss of activity. Radiolysis products of chloroform were shown to play an important role in the speciation of astatine forming both reactive and kinetically stable compounds. It was hypothesized that reactions with chlorine, as well as trichloromethyl hydroperoxide, forming polar astatine compounds are important reactions under the current experimental conditions.

Highlights

Astatine was first synthesized at UC Berkeley in 1940 by Corson, MacKenzie, and Segrè[1]
Astatine-211 dissolved in chloroform directly from elution after target recovery using dry distillation was found to be completely retained (101.2 ± 0.2%) during evaporation to dryness
If small activities of 131I dissolved in chloroform were evaporated to dryness, almost half of the activity (48 ± 5%) was released from the solvent. This result highlights the difference in chemistry between astatine and iodine, but could be a result of the large difference in dose delivered to the solvent during the two experiments

Summary

Introduction

Astatine was first synthesized at UC Berkeley in 1940 by Corson, MacKenzie, and Segrè[1] This method involves the bombardment of natural bismuth-209 with medium energy alpha particles in a cyclotron[1,2,3]. The half-life of astatine-211 is 7.2 h, which is long enough to allow for efficient labeling chemistry and compatibility with a number of different carrier vectors, compared, for example, to the half-life of bismuth-213, which is 46 minutes[5] It should, be noted that the known astatine-carbon bonds are relatively unstable in vivo, currently limiting systemic use of the nuclide[22]. One aspect, which is difficult to consider in basic chemical investigations, is the dense ionization of the media surrounding the short-lived alpha emitters This factor is important for understanding the chemistry relevant to nuclear medicine applications where high activities and high activity concentrations of the alpha particle emitting astatine-211 are used

Methods

Results

Conclusion