Removal of 238Pu(IV) from Mice by Poly-Catechoylate, -Hydroxamate or -Hydroxypyridinonate Ligands

Abstract

Binding of actinide (IV) by plasma proteins impedes excretion. Facilitation of elimination with chelating agents is the only known way to reduce carcinogenic risk. Iron-sequestering agents produced by micro-organisms contain metal-binding groups that bind Pu(IV) at pH 7.4 (catechol, CAM, in enterobactin; hydroxamate, X, in the ferrioxamines; hydroxpyridinone, HOPO). Our synthetic ligands contain up to four such groups linked by alkyl chains or attached to desferrioxamine (DFO) or diethylene-triamine-pentaacetic acid (DPTA). 238Pu excretion was tested in mice given 30 µmol.kg-1 of a ligand. Ligands that removed as much or more Pu than CaNa3-DTPA ((70% of injected Pu (% ID) are, in decreasing order of effectiveness: (1) Fe(III)-3,4,3-LIHOPO, (2) DFO-HOPO, (3) 3,4,3-LIHOPO, (4) 3,4,3-LICAM(C). Orally administered ligands 1-4, (5) 3,4,3-LICAM(S) and (6) ZnNa-DTPA-DX removed as much or more Pu than CaNa3-DTPA (( 15% ID). Ligands 1-4 and 6 injected 24 h after the Pu removed ( 5% ID more than control excretion (equivalent to or better than CaNa3-DTPA). All the new ligands at a dosage of 0.3 µmol.kg-1 removed a significant amount of Pu compared with controls: CaNa3-DTPA was ineffective. Ligand 3 is acutely toxic at high dosage, but the others appear to be of low toxicity. The HOPO ligands and ZnNa-DTPA-DX are recommended for further study.