Lloyd R D, Bruenger F W, Mays C W, Atherton D R, Jones C W, Taylor G N, Stevens W, Durbin P W, Jeung N, Jones E S
Radiat Res. 1984 Jul;99(1):106-28.
Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands has been investigated in beagles and mice. Eight dogs were injected intravenously (iv) with 237 + 239Pu(IV) + 241Am(III) citrate, and 30 min later, pairs of dogs were injected iv with 30 mumole/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetr aazatetradecane, tetrasodium salt], 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)te traazatetradecane, tetrasodium salt], CaNa3-DTPA, or each of the latter two ligands. Blood was sampled, and excreta were collected for 7 days, at which time the dogs were sacrificed and nuclide retention in liver and nonliver tissue was measured. Groups of five mice were each given 238Pu(IV) or 241Am(III) citrate iv; 3 min later 30 mumole/kg of a CAM ligand was injected intraperitoneally, mice were killed at 24 hr, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the four dogs injected once with 30 mumole/kg of LICAM(S).(ABSTRACT TRUNCATED AT 400 WORDS)
已在比格犬和小鼠中研究了四聚体儿茶酚酰胺（CAM）配体对钚（Pu）和镅（Am）的促排作用。8只犬静脉注射237 + 239Pu（IV）+ 241Am（III）柠檬酸盐，30分钟后，将犬两两分组，静脉注射30微摩尔/千克的3,4,3-LICAM（C）[N1,N5,N10,N14-四（2,3-二羟基-5-磺酰苯甲酰基）四氮杂十四烷四钠盐]、3,4,3-LICAM（S）[N1,N5,N10,N14-四（2,3-二羟基-4-羧基苯甲酰基）四氮杂十四烷四钠盐]、CaNa3-DTPA或后两种配体中的每一种。采集血液样本，并收集7天的排泄物，之后处死犬，测量肝脏和非肝脏组织中的核素滞留量。将每组5只小鼠静脉注射238Pu（IV）或241Am（III）柠檬酸盐；3分钟后腹腔注射30微摩尔/千克的一种CAM配体，24小时后处死小鼠，分析分离出的排泄物和组织。在犬中，注射的Pu和Am在7天时的平均滞留率分别如下：单独用CAM配体治疗后为12%和70%；用DTPA治疗后为30%和20%；用LICAM（S）加DTPA治疗后为12%和20%；未用配体时为90%和89%。在小鼠中，注射的Pu和Am的平均滞留率分别如下：用LICAM（C）治疗后为14%和66%；用LICAM（S）治疗后为21%和54%；未用配体时为91%和87%。在这两个物种中，DTPA或LICAM（S）在24小时内促进的净Pu排泄（有配体时的排泄 - 无配体时的排泄）中约99%在尿液中，而亲水性较差的LICAM（C）促进的净Pu排泄中约10%在粪便中。在所有用配体治疗的犬中，Am和Pu的排泄延迟都很显著。将用配体治疗的小鼠组织中的核素含量与核素注射后3分钟处死的小鼠组织中的核素含量进行比较，表明CAM配体螯合了循环中的Pu和Am并阻止了进一步沉积。此外，CAM配体清除了配体注射时肝脏和骨骼中可能存在的大部分可能松散结合的Pu。LICAM（C）在从肝脏中清除Pu方面更有效，而LICAM（S）在骨骼中更有效。在一次注射30微摩尔/千克LICAM（S）的4只犬中观察到中度至重度尿毒症以及肾脏远端小管中细胞杀伤的组织学证据。（摘要截断于400字）
