Development of Decorporation Agents for the Actinides

Chelation therapy for internally deposited actinides has been shown to reduce acute radiation damage and chemical toxicity and the severity of late radiation effects. This review traces the development of chelating agents for the actinides from the introduction of EDTA in the early 1950s, through the design and evaluation of multidentate ligands modelled after natural chelators of ferric iron, containing catecholate [CAM(S), CAM(C), MeTAM] or hydroxypyridinonate [1,2-HOPO, Me-3,2-HOPO] metal binding units. The most promising agents for in vivo chelation of plutonium, americium, and neptunium contain HOPO units, and the most efficient HOPO ligands are octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO). Tetradentate ligands with a linear 5-carbon backbone containing CAM(S), CAM(C), or Me-3,2-HOPO binding units are promising agents for decorporation of uranium.