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

作者：Ayed Tahra; Pilme Julien; Teze David; Bassal Fadel; Barbet Jacques; Cherel Michel; Champion Julie; Maurice Remi; Montavon Gilles^*; Galland Nicolas^*

来源：European Journal of Medicinal Chemistry, 2016, 116: 156-164.

DOI：10.1016/j.ejmech.2016.03.082

• Targeted radionuclide therapy
• Astatine
• Density functional theory
• Bond enthalpy
• In vivo stability

The application of At-211 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 At-211-labeled compounds and the At-R (R = C, B) bond enthalpies obtained from relativistic quantum mechanical calculations. Furthermore, we highlight important differences in the nature of the At-C and At-B 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 At-211, the proposed computational approach can readily be used to investigate bioactive molecules labeled with other heavy radionuclides.

• 出版日期2016-6-30