237Np:: Oxidation state in vivo and chelation by multidentate catecholate and hydroxypyridinonate ligands

Chemically, Np-237(V) is as toxic as U(VI), and radiologically, about as toxic as Pu-239. Depending on redox conditions in vivo, Np-237 exists as weakly complexing Np(V) (NpO2+) or as Np(IV), which forms complexes as stable as those of Pu(IV). Ten multidentate catecholate (CAM) and hydroxypyridinonate (HOPO) ligands with great affinity for Pu(IV) were compared with CaNa3-DTPA for in vivo chelation of Np-237. Mice were injected intravenously with (NpO2Cl)-Np-237: those in a kinetic study were killed 1 to 2880 min; in ligand studies, fed mice were injected intraperitoneally with a ligand 5, 60, or 1440 min after Np-237(V) (molar ratio 5.6 to 73), mice fasted for 16 h were gastrically intubated with a ligand 3 min after Np-237(V) (molar ratio 5.6 to 274), and all were killed 24 h after ligand administration; tissues and excreta were radioanalyzed. Rapid plasma clearance and urinary excretion of Np-237(V) resemble U(VI); deposition and early retention in skeleton and liver resemble Pu(IV). The x-ray absorption near edge structure spectroscopy (XANES) spectra of femora of Np-237(V)-injected mice, compared with spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV). Significant in vivo Np-237 chelation was obtained with all of the HOPO and CAM ligands injected at molar ratio 22; the HOPO ligands reduced Np-237 in skeleton, liver, and other soft tissue, on average, to 72, 25, and 25% of control, respectively, while CaNa3-DTPA was ineffective. Two HOPO ligands injected 60 min after Np-237 (molar ratio 5.6) significantly reduced body and liver Np-237, and three HOPO ligands given orally (molar ratio greater than or equal to 73) significantly reduced body and liver Np-237, compared with controls. Combined with earlier work, these results indicate that: the dominant neptunium species circulating and excreted in urine is Np(V), while that in bone and liver deposits is Np(IV); Np(V) must be reduced to Np(IV) before it can be stably chelated; efficient decorporation of neptunium requires multidentate ligands that form exceptionally stable actinide(IV) chelates and facilitate Np(V) reduction.