Chelation Therapy of Thorium Deposited in Rat Lung

Rencová, J.; Volf, V.; Burgada, R.

doi:10.1093/oxfordjournals.rpd.a032449

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Improved synthesis of 3,4,3-LI(1,2-HOPO) (Uhlir 1992;Bailly and Burgada 1998;Xu et al 2002) permitted extended studies in rats in a variety of exposure (actinide injection or inhalation) and treatment protocols. Reductions of Pu(IV) and Th(IV) in bone and tissues (including the lungs) by 3,4,3-LI(1,2-HOPO) were superior to CaNa 3 -DTPA in all of the combinations of exposure and treatment protocols (Stradling et al 1991b(Stradling et al , 1992Volf et al 1993Volf et al , 1996bPoncy et al 1993;Paquet et al 1994;Stradling 1994Stradling , 1998Rencova et al 1998).…”

Section: 43-li(12-hopo)mentioning

confidence: 99%

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Durbin¹

2008

Health Physics

106

View full text Add to dashboard Cite

All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage.

show abstract

Section: 43-li(12-hopo)mentioning

confidence: 99%

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Durbin¹

2008

Health Physics

106

View full text Add to dashboard Cite

show abstract

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

Luo

Sun

et al. 2005

International Journal of Radiation Biology

View full text Add to dashboard Cite

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.

show abstract

Chelation Therapy of Thorium Deposited in Rat Lung

Cited by 2 publications

References 0 publications

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

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

Contact Info

Product

Resources

About