Towards elucidating the radiochemistry of astatine – Behavior in chloroform

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.

Radiolabeling chemistry with heavy halogens iodine and astatine

“…Radiolysis arises from 211 At highly energetic alpha decay, forming degradation products (radicals and highly reactive recombination compounds). As radiolysis is correlated to the irradiation dose received by the solution, radiolabeling chemistry with 211 At is challenging, especially at high level of activity or when there is a delay between At production and its use (Aneheim et al, 2019;Pozzi and Zalutsky, 2007).…”

Guest Edited Collection: Radioisotopes and radiochemistry in health science

“…While the lightest halogen has become the workhorse of PET imaging, the heaviest (natural) halogen, astatine, has been advancing as a therapy agent. This Collection includes reports on optimized 209 Bi(α,2n) cyclotron production and recovery of targeted alpha therapy (TAT) isotope 211 At (7.2 h) 23,24 and an investigation into astatine's solvent extraction behaviour 25 . Radioiodine still plays an important role; beyond historic 131 I, other iodine isotopes 26 are now utilized for SPECT imaging ( 123 I, 13.3 h) and treatment (Auger emitter 125 I, 59.4 d).…”

Investigating the Heaviest Halogen: Lessons Learned from Modeling the Electronic Structure of Astatine's Small Molecules

“…[3][4][5][6] However, 211 At's scarcity due to production complexity and cost keeps its experimental chemistry elusive, thus creating a major obstacle in translating accelerator-generated elemental 211 At to radiopharmaceuticals. 7 The absence of spectroscopic data even for diatomic species, such as At 2 , HAt, or AtO + , leaves state-of-the-art ab initio quantum-chemical calculations the sole source of basic reference data on the equilibrium internuclear distance R e , dissociation energy D e , and vibrational frequency ω e . As a heavy element, astatine exhibits strong relativistic effects that extend to its valence electrons.…”