双分子取代苯酚氨羧酸螯合剂对放射性钍促排活性的 …

目的 对已合成的１５个双分子取代苯酚氨羧酸螯合剂经动物实验观察对＾２３４Ｔｈ的促排活性,以探讨化学结构与促排活性的构效关系。方法 以大鼠尿,粪中＾２３４Ｔｈ排出量的增高,组织（肝,骨）中蓄积量的降低与对照组比较作为评价指标。结果 １５个螯合剂中除４个外均显示不同程度的促排活性,其中有３个其尿,粪中＾２３４Ｔｈ的排出量达６０％－７０％,肝,骨中＾２３４Ｔｈ析蓄积量明显降低。     

双分子取代苯酚类螯合剂的合成及对放射性钍的促排效果研究

目的本文旨在寻找新的治疗用螯合剂，以加速排除沉积在体内的放射性钍，达到放射防护的目的。方法首先通过Ｍａｎｎｉｃｈ反应合成双分子取代苯酚类螯合剂，然后经动物实验：ＳＤ大鼠静脉中毒２３４Ｔｈ后立即肌注药物，２天后解剖动物测定２３４Ｔｈ量，计算排出量和蓄积量，研究其促排效果。结果所报道的螯合剂不仅能增加大鼠在尿、粪中２３４Ｔｈ的排除，同时能降低在肝、骨中的蓄积，呈现较好的促排效果。其中以化合物Ⅷ促排效果最好，２天后可排除６８％的２３４Ｔｈ；在肝、骨中的沉积仅为１１．７％，而对照组则是８７．６％。结论螯合剂Ⅷ值得进一步研究探讨。     

双分子取代苯酚类螯合剂的合成及对放射性钍的促排…

本文旨在寻找新的治疗用螯合剂，以加速排除沉积在体内的放射性钍，达到放射防护的目的，方法 首先通过Ｍａｎｎｉｃｈ反应合成双分子取代苯酚类螯合剂，然后经动物实验：ＳＤ大鼠静脉中毒＾２３４Ｔｈ后立即肌注药物，２天后解剖动物测定＾２３４Ｔｈ量，计算排出量和蓄积量，研究其促排效果。结果 所报道的螯合剂不仅能增加大鼠在尿、粪中＾２３４Ｔｈ的排除，同时能降低在肝，骨中的蓄积，呈现较好的促排效果。其中以化合物Ⅷ促     

邻苯二酚氨羧酸螯合剂对钍内污染早期给药效果

目的 研究邻苯二酚氨羧酸螯合剂的促排^234Th的效果和抗自由基作用在防护核素内照射损伤中的作用关系。方法 首先确定小鼠ip中毒^234Th致内照射损伤的剂量和时间，选择0.6MBq／鼠的中毒剂量ip后，立即im螯合剂，连续3d，并以DTPA和VitE作促排效果和抗自由基作用的阳性对照，第4天处死动物，观察整体和肝、骨中^234Th蓄积量，骨髓有核细胞数(BMNC)，骨髓、肝脏和血清脂质过氧化产物丙二醛(MDA)含量及骨髓和肝脏的病理变化。结果 小鼠ip^234Th0.6MBq／鼠第4～8天，骨髓和肝脏出现明显的内照射损伤。给予螯合剂9501、7601和DTPA后，均有明显的促排作用，使整体中^234Th蓄积量比中毒组分别下降81％、86％和72％，以第一次用药效果最为明显；肝、骨中总的^234Th蓄积量分别仅为中毒组的22％、21％和58％，其中9501、7601的效果明显优于DT—PA，骨中蓄积量仅为DTPA的1／3～1／5。9501和7601立即给药未观察到^234Th急性中毒后的内照射损伤，BMNC数、骨髓MDA含量正常，骨髓、肝脏未见明显的病理改变。DTPA组可见骨髓组织轻度受损。给予VitE未能减轻骨髓、肝组织的内照射损伤，可能由于在短时间内核素大量蓄积于组织中所致。VitE和DTPA合并用药，显示DTPA的促排活性和VitE的抗氧化作用。结论 9501和7601立即给药对核素内照射损伤有明显的防护作用，主要是由于其显著的促排作用。     

邻苯二酚氨羧酸螯合剂对钍内污染延缓给药的效果

目的 进一步确证邻苯二酚氨羧酸螯合剂在体内的抗自由基作用，增进对核素内照射损伤的防护效果，及与促排效果之间的关系。方法 小鼠ip^234Th0．6MBq／鼠3d后im螯合剂，连续3d，并以DTPA和VitE作促排效果和抗自由基作用的阳性对照，第8天处死动物检测整体和肝、骨中^234Th蓄积量，骨髓有核细胞计数，骨髓、血清、肝匀浆MDA含量，观察骨髓、肝脏组织的病理变化。结果 9501、7601、DTPA延缓给药均仍有明显的促排效果，使整体^234蓄积量比中毒组下降15％～16％，肝、骨蓄积量下降分别为中毒组的77％-79％和72％～75％，三者的效果相比差异无显著性，但明显低于即刻用药的效果。9501和7601能明显减轻^234Th内污染小鼠的辐射损伤，骨髓有核细胞数，骨髓、肝脏MDA含量正常，未见明显的骨髓、肝脏的病理改变。而DTPA组的防护效果较差．出现较明显的骨髓组织损伤。VitE给药后第8天对减轻^234Th所致骨髓、肝脏内照射损伤有一定的效果。结论 9501和7601对核素内照射损伤有明显的防护效果，具有促排和抗自由基作用的双重功能，是2个较理想的螯合剂，值得进一步研究。     

螯合剂BPCBG对急性铀中毒大鼠的促排效果及肾损伤的保护作用

目的 探讨螯合剂BPCBG对急性铀中毒大鼠促排作用的量-效和时,效关系以及对铀致肾损伤的保护作用.方法 Sprague-Dawley( SD)雄性大鼠按随机数字表法分为正常对照组、铀中毒组、不同剂量BPCBG组和DTPA-CaNa3组.给药组大鼠于腹腔注射醋酸铀酰(100μg/只)后,立即分别肌肉注射60、120和600μmol/kg BPCBG及120和600μmol/kg DTPA-CaNa3,或于注射醋酸铀酰前0.5和2h、铀中毒后0、0.5、1及2h肌肉注射120 μmol/kg BPCBG,铀中毒组于注射醋酸铀酰后立即注射等体积生理盐水,正常对照组仅注射生理盐水.采用ICP-MS方法检测24 h尿铀排出量和肾、骨中铀蓄积量.大鼠注射醋酸铀酰(500 μg/只)后立即注射600 μmol/kg BPCBG和1200 μmol/kg DTPA-CaNa3,48 h后检测血清肌酐(SCR)与尿素氮(BUN)含量,取一侧肾脏做肾组织病理切片观察.结果 铀中毒后立即注射不同剂量BPCBG(60、120和600 μmoL/kg)使24h尿铀排出量比铀中毒组增加(t =2.22、4.43、5,80,P＜0.05),肾和骨铀蓄积量下降(t.3.33、5.59、4.53,P＜0.01和t=2.15、8.70、9.10,P＜0.05),随给药剂量增加促排效果明显提高.提前0.5h或延迟0.5和1h给予BPCBG,仍有较好的排铀效果(与铀中毒组比较,尿铀排出量:提前0.5 h t=4.34,延迟0.5 ht=3.35,P＜0.05;肾铀蓄积量:t=5.75、7.74、5.87,P＜005:骨铀蓄积量:t=6.43、5.22、2.60,P＜0.05),但随铀中毒和给药间隔时间的延长而下降.BPCBG立即给药能明显减轻铀中毒致肾脏的病理损伤,使SCR及BUN含量降低至正常对照组水平,对铀致肾功能损伤具有保护作用.DTPA-CaNa3虽然能明显降低大鼠肾铀蓄积量(与铀中毒组相比,120和600-μmol/kg,t =2.28、3.35,P＜0.05),但未能显著增加尿铀排出量,骨铀蓄积量还有增加趋势,并且对铀致大鼠肾损伤无保护作用.结论 BPCBG对急性铀中毒大鼠有良好的促排效果与肾脏保护作用,有可能成为一种新型铀促排螯合剂.     

苯酚氨羧酸类螯合剂对放射性核素加速排除效果的研究

动物实验表明取代苯酚、苯二酚等氨羧酸螯合剂对放射性核素¹⁴⁴Ce,²³⁴Th都有较好的促排效果。这类螯合剂的促排效果与结构有密切关系。本文对合成的27个螯合剂的构效关系研究初步表明:邻苯二酚化合物优于对,间苯二酚化合物。邻、间、对苯二酚审一个羟基代之以其它基因的化合物如邻取代苯酚化合物其效果下降,对、间代苯酚化合物效果有所提高,但不及邻苯二酚类效果好。     

五种络合剂对促排钍的疗效评价

本文对有较好排钍效果的811、8102、8307-7603和DTPA等五种络合剂, 从量效关系, 时效关系和疗效强度等方面进行比较。结果表明, 从尿粪中²³⁴Th的排出量的增加和组织中²³⁴Th蓄积量的降低为指标, 以8102的疗效为最佳, 其次是811, 但811使肾²³⁴Th菩积量有增加。DTPA和7603在高剂量时才有较好的排²³⁴Th效果, 且7603以粪²³⁴Th形式排出为主, 其疗效与DTPA、8307基本相当。     

喹胺酸和LICAM(C)对大鼠体内238Pu和241Am的促排效果比较

喹胺酸(Quinamic acid, QAA, 811)是一种异哇啉类络合剂, 对钍有较好的促排效果。本文主要研究大鼠静脉注入(iv)²³⁸Pu和²⁴¹Am各26kBq/kg后1小时, 经皮下注入(so)不同剂量.(1～30μmol/kg)QAA, 或静脉注入核素后立即灌胃(po)QAA(30μmol/kg)对²³⁸Pu、²⁴¹Am的促排疗效, 并与LICAM(C)相比较。实验观察到QAA对降低骨肝中²³⁸Pu、²⁴¹Am的蓄积量有较好的作用, QAA对²³⁸Pu的促排效果高于对²⁴¹Am.在剂量(1～30μgmol/kg)对肝、肾中²³⁸Pu和骨、肾中²⁴¹Am蓄积量的降低, QAA优于LICAM(C)；灌胃QAA(30μttmol/kg)伍用NaHCO₃(5mmol/kg的)疗效, 对骨、肝中²³⁸Pu蓄积量的降低, QAA和LICAM(C)二间无差异(P>0.05), 但对²³⁸Pu在肾中蓄积量和对²⁴¹Am在骨, 肾中蓄积量的降低, QAA明显优于LICAM(C)。     

^99mTc直接标记抗体用于放免显像时放射性本底的促排

９９ｍＴｃ直接标记抗体用于放免显像时放射性本底的促排李宏利吴永慧刘元方附表ＥＣ、ＭＡＧ３对小鼠各器官、组织％ＩＤ／ｇ促排下降程度（％）促排剂促排时间（ｈ）处死时间（ｈ）血心肺肝脾肾肠胃骨肌肉ＥＣ２６３２８２６４２００１４２０７２４３３１...     

Decorporating efficacy of catecholaminocarboxylate chelating agents for thorium-234 and protective effects on associated radiation injury

The aim was to identify the decorporation and anti-oxidation efficacy of prompt and delayed consecutive administration of the catecholicpolyaminopolycarboxylate ligands 9501 and 7601 for radiothorium in vivo. The chelating agents 9501 or 7601 were administered intramuscularly to ICR mice 3 min or 3 days after intraperitoneal injection of 30 MBq kg(-1) (234)Th-citrate for 3 consecutive days. The animals were killed 4 or 5 days after administration of the chelating agents, respectively. The (234)Th radioactivity in the whole-body and its retention in liver and skeleton were determined. Malondialdehyde (MDA) production, as an index of (234)Th-induced lipid peroxidation in bone marrow and liver, was assayed and the number of bone marrow nucleated cells (NBMNC) were counted. The pathological changes of bone marrow and liver tissue were observed. CaNa(3)-diethylenetriaminepentaacetate (DTPA) and vitamin E were used as controls. The competitive ability of 9501 and 7601 to mobilize thorium with bovine serum albumin (BSA) was studied. Their inhibitory effect on superoxide anion radicals was measured by electron spin resonance. When promptly injected, 9501 or 7601 were superior to CaNa(3)-DTPA for reducing (234)Th retention in mouse. Their different bioactivity for decorporation of (234)Th was consistent with their competitive ability to mobilize thorium with BSA. Although the removal effectiveness of 9501 and 7601, given by delayed injection, was lower than that of the prompt administration, they could inhibit (234)Th-induced lipid peroxidation. This caused significant reductions of MDA content in bone marrow and liver and markedly ameliorated histological changes to bone marrow and liver tissue in (234)Th-treated mice. Their protective effects were better than CaNa(3)-DTPA and vitamin E. 9501 and 7601 could directly scavenge O(.-)(2). Their effects as O(.-)(2) scavengers were very significant. The chelating agents 9501 and 7601 are able to remove thorium as effectively as other commonly used agents like CaNa(3)-DTPA and reduce radiation dose. In addition, these agents have anti-oxidative action reducing both cell killing in the bone marrow and malondialdehyde levels, a measure of lipid peroxidation, in the bone marrow and liver. The protection from internally deposited radioactive material was predictable by the chelators' competitive ability to chelate thorium from BSA and their ability to act as an oxygen free-radical scavenger. The duel effect of reducing radiation dose and response could be important in reducing the risk from internally deposited gamma radionuclides.     

Whole-body distribution of americium in rats for different pathways of intake

Abstract

Purpose: To compare data on the whole-body distribution of americium-241 (²⁴¹Am) in rats following intravenous injection (IV), inhalation, and wound (intramuscular injection, IM).

Material and methods: Following exposure, each rat was placed in an individual metabolism cages for the duration of the study, 28 days (d). Urine and feces were collected daily. Tissues and organs were collected and measured.

Results: Liver and skeleton were the main sites of deposition for all routes of exposure but the content differed substantially. By 28 d, ²⁴¹Am content in liver was similar for IV and IM administrations (12 ± 4% and 14 ± 5%, respectively), which was 3-fold higher compared to inhalation. Americium-241 content in skeleton was 27% by the end of the IV study; which was 50% higher compared to the IM study and 6-fold higher compared to inhalation. The cumulative excretion in 28 d was 54% for IV (44% by feces and 10% by urine); 38% for IM (34% by feces and 4% by urine); and 84% for inhalation (83% by feces and 1% by urine).

Conclusion: Unperturbed rat models for the three routes of administration are the baseline for evaluating the efficacy of chelating agents.     

The biokinetics and radiotoxicology of curium: a comparison with americium

The human and animal data on the biokinetics of (242)Cm and (244)Cm are reviewed and shown to be very similar to those for (241)Am. Liver and skeleton are the main organs of deposition and the retention of curium in the skeleton is very prolonged in all the species examined. Retention of both curium and americium in the liver appears to be species-dependent, being relatively rapidly removed from the liver of rats, and probably humans, but being tenaciously retained in dogs and some other species. The radiotoxicity of curium is also reviewed and it is shown that, as with (241)Am, lung and bone tumour induction are the major hazards from inhaled and systemically deposited (244)Cm. The use of chelating agents for the treatment of accidental contamination of the human body with (242,244)Cm is also discussed.     

Influence of heavy metals upon the retention and mobilization of polonium-210 in rats

PURPOSE: To provide information about the tissue retention and mobilization of the alpha-emitting radionuclide, polonium-210 (210Po), in rats under combined exposure to heavy metal ions and the chelating agent, 2, 3-dimercaptopropane-1-sulfonate (DMPS). MATERIALS AND METHODS: Rats were pre-exposed intraperitoneally to either CdCl2 or Pb(CH3COO)2. 9 or 15 h later they received 210Po nitrate intravenously. The retention and excretion of 210Po via the urine and faeces of pre-exposed rats, as well as in pre-exposed rats treated with DMPS, were followed. The radioactivity due to 210Po in a broad spectrum of body tissues and excreta was measured by the liquid scintillation counting after sample digestion in a mixture of perchloric acid and hydrogen peroxide. The immunohistochemical localization of metallothioneins (MT) was studied using a mixture of murine monoclonal antibodies directed against MT I+II. RESULTS: The present study revealed different tissue distributions of polonium-210 in the rats pre-exposed to lead or cadmium ions when compared with that in 210Po only controls. Under combined exposure to Pb or Cd, the spontaneous excretion of 210Po was enhanced and could be further enhanced by treatment with DMPS. Treatment with this chelator was efficient even when its start was postponed until 24h after internal contamination of the body with 210Po. CONCLUSIONS: Polonium-210 is bound in vivo to binding sites on various biomolecules, among them erythrocytic enzymes and MT. This phenomenon explains the different affinity and overall distribution of 210Po in control body tissues. When the appropriate binding sites are occupied by lead or cadmium, enhanced natural excretion of polonium-210 occurs.     

Decorporation of radionuclides investigations on the pharmacokinetics of DTPA by means of its decorporating effect on 144Cer (author's transl)]

The influence of Zn-DTPA on the retention of 144Cer in several organs of the rat was investigated 4 days after 144Cer application either with intact or with prevented renal excretion. As the 144Cer activity mobilized from the liver is recovered in gut and faeces an excretion of DTPA bount 144Cer with the bile can be assumed. In animals with impeded renal function an amount of 144Cer is accumulated in blood and extracellular water which corresponds to that mobilized from the skeleton and is normally excreted with the urine.     

Radiation dose to the human body from intravenously administered 75Se-sodium selenite.

The dose of radiation to the human body and some of its organs after intravenous administration of 75Se-sodium selenite for diagnostic purposes has been calculated on the basis of followup of 26 patients for as long as 517 days with measurements of: 1. The retention of 75Se in the whole body. 2. The retention of 75Se in the blood, liver, kidneys, ovaries, testicles, and hair. 3. The excretion of 75Se in urine and feces. Whole-body counting and profile scanning were done on the patients and samples of blood from different organs, urine, and feces were measured for radioactivity. The dose of radiation received was calculated for an average patient of 70 kg. These doses were found to be slightly higher than previously reported on a smaller number of patients and with a shorter follow-up. They were slightly lower than those from 75Se-methionine to the whole body but higher to the liver and kidneys. The margin of error in this investigation was estimated to be about 20% for the whole-body dose and probably higher for different organs, mostly due to the poorly known rate of retention of selenite in different organs.