In Vivo Chelation of Am(III), Pu(IV), Np(V), and U(VI) in Mice by TREN-(Me-3,2-HOPO)

Octadentate 3,4,3-LI(1,2-HOPO), composed of the acidic hydroxypyridine isomer, 1,2-HOPO, is the most effective ligand yet prepared for in vivo chelation of Pu(IV), and Am(III), but it is difficult to prepare and acutely toxic at high dosage. Hexadentate TREN-(Me-3,2-HOPO), composed of the less acidic Me-3,2-HOPO isomer, can be produced in relatively large quantities. Tren-(Me-3,2-HOPO) (30 µmol.kg-1 injected intraperitoneally in mice 3 min to 1 h after intravenous injection of an actinide) removed significant body Pu(IV), Am(III), Np(V), or U(VI) (compared with controls), and those actinide reductions were significantly greater than were obtained with CaNa3-DTPA. TREN-(Me-3,2-HOPO) was almost as effective for reducing body Pu(IV) as 3,4,3-LI(1,2-HOPO). TREN-(Me-3,2-HOPO) is of low acute toxicity in mice and its clinical potential, as a practical compromise between the effectiveness of 3,4,3-LI(1,2-HOPO) and the safety of CaNa3-DTPA, merits further investigation.