Exploration of a new radiolabeling pathway with astatine-211 of monosubstituted alkynes: feasibility studies and stability evaluation

Astatine-211, a very promising radioisotope for nuclear medicine, is a halogen and a 100% alpha emitter, making him one of the best candidates for radiotherapy. However, it is only available in trace concentrations and the current astatine-aryl compounds undergo de-astatination during the internalization in cells. To overcome this issue, we investigated a strategy based on astatine-alkyne that is expected to be more resistant to de-astatination based on quantum chemical calculation. An iodonium salt-based precursor of astatine-alkyne was designed. Radiolabeling and purification were set up and optimized for astatine-alkyne. Then, the astatine-alkyne stability was compared in different media with ethyl 3-astatine-benzoate, used as reference. The (astatine-ethynyl)benzene is, to our knowledge, the first reported that contains a C(sp)-At bond. With this compound, we obtained > 85% radiochemical yield within less than 30 min at room temperature with a radiochemical purity of > 95%. The in vitro stability assays highlighted an instability, especially in human blood serum, with release of free astatine, while the SAB analogous remained stable in those conditions. The radioiodinated analogous to the astatine-alkyne compound exhibited the same instability. The triple C-C bond may be responsible for the instability. A simple model was made to understand the instability of halogen-alkynes, and thiols may explain partially the degradation observed in human blood serum. (author)