Radiolabeling yield dependency of post-dry distillation decay of astatine-211

Astatine-211 (²¹¹At) is one of the most promising nuclides for targeted alpha therapy. However, while several clinical trials are ongoing worldwide, some aspects of the element remain unexplored. This work aims to investigate changes in radiochemical yield over time, expressed as the number of ²¹¹At decays, post-dry distillation using two common astatination reactions.

²¹¹At was purified from activated bismuth targets via dry distillation and eluted in chloroform. The solvated activity was then either evaporated to dryness or left in the chloroform eluate. Before chemical reactions, both forms of the starting material were allowed to age at room temperature for up to 28 h, correlating to 3 ∙ 10^{12 211}At decays. All chemical reactions were subsequently started from a dry residue. Radiolabeling was carried out either via electrophilic destannylation of tri(methyl)phenylstannane, or via the nucleophilic substitution of bis(4-tert-butylphenyl)iodonium p-toluenesulfonate. Radiochemical yield was determined using a dual flow radiodetection HPLC method allowing direct yield quantification.

In both cases, where ²¹¹At was stored either as a dry residue or in chloroform, radiochemical yields decreased with increasing amounts of radioactive decay. This was true both for nucleophilic and electrophilic astatinations. In the case of ²¹¹At stored in chloroform, the dose-yield relationship indicates a more rapid decrease for electrophilic astatination. However, decreases in radiochemical yield could be mitigated by increasing the precursor concentration, keeping yields constant above 80 % even when using ²¹¹At after 28 h, corresponding up to 3 ∙ 10^{12 211}At decays. There is also an indication that higher amounts of oxidizing/reducing agents and redissolution of dry ²¹¹At in fresh chloroform may mitigate the loss in yield to some extent.

Radiochemical yields in labeling with ²¹¹At decrease over time post dry distillation independent if the ²¹¹At was kept dry or in chloroform. If high specific activity is a requirement for the final radiolabeled product, the most reliable way to maintain high yields is to perform the radiolabeling close in time after the dry distillation.