A novel method for producing astatine-based cancer therapeutics

2020

Challenge

Alpha particles emitted by radioactive compounds are known to destroy tumor cells effectively without harming healthy tissues. However, incorporating radioactive isotopes into cancer therapeutics presents numerous challenges, including low yields and unstable links between the therapeutic compound and the isotope.

Advance

A group of IRP researchers led by Yong Sok Lee, Ph.D., François Guerard, Ph.D., and Martin Brechbiel, Ph.D., in collaboration with colleagues at Université de Nantes in France, developed a novel method of incorporating a radioactive isotope of the element astatine (At) into small molecules. Their approach successfully introduced the isotope, 211At, into a pharmaceutical far more efficiently than conventional approaches and resulted in consistent yields of the compound. When linked to cancer-targeting antibodies, 211At has the potential to more effectively deliver cancer-killing alpha particles to tumors in cancer patients.

Impact

With the growing capacity of producing 211At worldwide, the IRP researchers’ patented technology can be effectively applied to treating cancer patients. Clinical trials are now being planned in France based on their approach to producing cancer-targeting antibodies labeled with 211At.

Publications

Guérard F, Gestin JF, Brechbiel MW, Lee YS. (2020). Method for Synthesizing Iodo- or Astatoarenes Using Diaryliodonium Salts. U.S. Patent No: 10703708.

Guérard F, Navarro L, Lee YS, Alliot C, Chérel M, Brechbiel MW, Gestina JF. (2017). Bifunctional Aryliodonium Salts for Highly Efficient Radioiodination and Astatination of Antibodies. Bioorg Med.Chem. Nov 1;25(21):5975-5980.

Guérard F, Lee YS, Baidoo K, Gestin JF, and Brechbiel MW (2016). Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts. Chem.-A. Eur. J. Aug 22;22(35):12332–12339.