Durbin P W, Kullgren B, Xu J, Raymond K N, Allen P G, Bucher J J, Edelstein N M, Shuh D K
Chemical Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Health Phys. 1998 Jul;75(1):34-50. doi: 10.1097/00004032-199807000-00007.
Chemically, 237Np(V) is as toxic as U(VI), and radiologically, about as toxic as 239Pu. Depending on redox conditions in vivo, 237Np 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 237Np. Mice were injected intravenously with 237NpO2Cl: 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 237Np(V) (molar ratio 5.6 to 73), mice fasted for 16 h were gastrically intubated with a ligand 3 min after 237Np(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 237Np(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 237Np(V)-injected mice, compared with spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV). Significant in vivo 237Np chelation was obtained with all of the HOPO and CAM ligands injected at molar ratio 22; the HOPO ligands reduced 237Np 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 237Np (molar ratio 5.6) significantly reduced body and liver 237Np, and three HOPO ligands given orally (molar ratio > or = 73) significantly reduced body and liver 237Np, 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.
从化学性质上讲，237Np(V) 的毒性与U(VI) 相当，从放射学角度看，其毒性约与239Pu 相当。根据体内的氧化还原条件，237Np 以弱络合的Np(V)（NpO2+）形式存在，或以Np(IV) 形式存在，Np(IV) 形成的络合物与Pu(IV) 的络合物一样稳定。将10种对Pu(IV) 具有高亲和力的多齿儿茶酚（CAM）和羟基吡啶酮（HOPO）配体与CaNa3-DTPA 进行比较，以研究它们对237Np 的体内螯合作用。给小鼠静脉注射237NpO2Cl：动力学研究中的小鼠在1至2880分钟后处死；在配体研究中，喂食的小鼠在237Np(V) 注射后5、60或1440分钟腹腔注射一种配体（摩尔比为5.6至73），禁食16小时的小鼠在237Np(V) 注射后3分钟经胃插管给予一种配体（摩尔比为5.6至274），所有小鼠在给予配体24小时后处死；对组织和排泄物进行放射性分析。237Np(V) 的快速血浆清除和尿排泄类似于U(VI)；在骨骼和肝脏中的沉积和早期滞留类似于Pu(IV)。与参考固体中Np(V) 和Np(IV) 的光谱相比，注射237Np(V) 的小鼠股骨的X射线吸收近边结构光谱（XANES）主要显示为Np(IV)。以摩尔比22注射所有HOPO和CAM配体均获得了显著的体内237Np螯合效果；HOPO配体平均将骨骼、肝脏和其他软组织中的237Np分别降低至对照的72%、25%和25%，而CaNa3-DTPA 无效。与对照组相比，在237Np 注射60分钟后注射两种HOPO配体（摩尔比为5.6）显著降低了体内和肝脏中的237Np，口服三种HOPO配体（摩尔比≥73）显著降低了体内和肝脏中的237Np。结合早期的研究工作，这些结果表明：尿液中循环和排泄的主要镎物种是Np(V)，而骨骼和肝脏沉积物中的主要镎物种是Np(IV)；Np(V) 在能够被稳定螯合之前必须还原为Np(IV)；有效的镎促排需要多齿配体，这些配体形成异常稳定的锕系元素(IV) 螯合物并促进Np(V) 的还原。
