(211)At-labeled agents for alpha-immunotherapy: On the in vivo stability of astatine-agent bonds.

The application of 211 At to targeted cancer therapy is currently hindered by the rapid deastatination that occurs in vivo. As the deastatination mechanism is unknown, we tackled this issue from the viewpoint of the intrinsic properties of At-involving chemical bonds. An apparent correlation has been evidenced between in vivo stability of 211 At-labeled compounds and the AtAR (R ¼ C, B) bond enthalpies obtained from relativistic quantum mechanical calculations. Furthermore, we highlight important differences in the nature of the AtAC and AtAB bonds of interest, e.g. the opposite signs of the effective astatine charges, which implies different stabilities with respect to the biological medium. Beyond their practical use for rationalizing the labeling protocols used for 211 At, the proposed computational approach can readily be used to investigate bioactive molecules labeled with other heavy radionuclides.