Octadentate Hydroxypyridinonate (HOPO) ligands for plutonium (IV): Pharmacokinetics and oral efficacy

Linear octadentate spermine based 3,4,3-LI(1,2-HOPO) and the mixed ligand, 3,4,3-LI(1,2-Me-3,2-HOPO), are the most effective agents for decorporation of Pu prepared so far; they are effective at low dosage, orally active, and of low toxicity at effective injected dosage. Their pharmacological properties are favourable for in vivo Pu chelation - penetration of extracellular water, useful residence in the circulation, substantial hepato-biliary excretion, low but useful GI absorption, and transitory residence in the kidneys. Reductions of body Pu were significant, compared with controls, when oral administration to normally fed mice (30 or 100 µmol kg-1) was delayed as long as 24 h after iv Pu injection. The HOPO ligands (10-100 µmol kg-1) or CaNa3-DTPA (100 or 300 µmol kg-1) were given orally to normally fed mice starting at 4 h after an iv Pu injection and continued 5 d per week for 3 weeks. 3,4,3-LI(1,2-HOPO) (100 µmol kg-1) reduced Pu in skeleton, liver, and body, to 44 ± 9, 18 ± 8, and 38 ± 7% of controls, respectively, reductions significantly greater than with the mixed HOPO ligand or with three times more CaNa3-DTPA.