Ayed Tahra, Pilmé Julien, Tézé David, Bassal Fadel, Barbet Jacques, Chérel Michel, Champion Julie, Maurice Rémi, Montavon Gilles, Galland Nicolas
CEISAM, CNRS UMR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France.
Sorbonne Universités, UPMC Université Paris 06, UMR 7616, Laboratoire de Chimie Théorique, F-75005 Paris, France; CNRS UMR 7616, Laboratoire de Chimie Théorique, F-75005 Paris, France.
Eur J Med Chem. 2016 Jun 30;116:156-164. doi: 10.1016/j.ejmech.2016.03.082. Epub 2016 Mar 29.
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 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 (211)At, the proposed computational approach can readily be used to investigate bioactive molecules labeled with other heavy radionuclides.
目前，（211）砹在靶向癌症治疗中的应用受到其在体内快速脱砹现象的阻碍。由于脱砹机制尚不清楚，我们从含砹化学键的内在性质角度解决了这个问题。（211）砹标记化合物的体内稳定性与通过相对论量子力学计算得到的At-R（R = C、B）键焓之间已证明存在明显的相关性。此外，我们强调了所关注的At-C键和At-B键性质的重要差异，例如有效砹电荷的相反符号，这意味着在生物介质中具有不同的稳定性。除了在合理化用于（211）砹的标记方案方面的实际用途外，所提出的计算方法可很容易地用于研究用其他重放射性核素标记的生物活性分子。
