Early Chelation Therapy for Injected Pu-238 and Am-241 in the Rat: Comparison of 3,4,3-LIHOPO, DFO-HOPO, DTPA-DX, DTPA and DFOA

Volf, V.; Burgada, R.; Raymond, K.N.; Durbin, Patricia W.

doi:10.1080/09553009314552191

Cited by 28 publications

(59 citation statements)

References 14 publications

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“…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: 94%

“…It was effective for in vivo Pu(IV) chelation at low dosage, when given orally or infused or when injection was delayed. It was significantly less effective than CaNa 3 -DTPA for reducing Pu(IV) in the lungs and tissues of rats that had inhaled 238 Pu(IV) nitrate (White et al 1988;Durbin et al 1989a;Stradling et al 1991a;Volf et al 1993Volf et al , 1996b. The weak acidity of the hydroxamic acid groups may prevent DFO-(1,2-HOPO) from stably binding Pu(IV) in the low pH environment of the lungs.…”

Section: Dfo-(12-hopo)mentioning

confidence: 95%

“…Multidentate ligands containing catecholate [CAM(C), CAM(S)] or hydroxamate (DFOM) are ineffective for Am(III) decorporation (Taylor 1967;Volf et al 1977Volf et al , 1993Volf et al , 1996bLloyd et al 1984;Stradling et al 1986Stradling et al , 1989Stradling et al , 1991aVolf 1986). The Am(III) complexes with those ligands are weak.…”

Section: Catecholate and Hydroxamate Ligandsmentioning

confidence: 97%

“…Mice or rats injected with 241 Am(III) citrate were given HOPO ligands by injection or orally, and all markedly reduced Am(III) in bone and soft tissues compared with controls and promoted significantly more Am(III) excretion than an equimolar amount of CaNa 3 -DTPA (Table 4) (Stradling et al 1992;Volf et al 1993;Durbin et al 1994). In rats injected with Am(III) im or sc, 3,4,3-LI(1,2-HOPO), TREN-(Me-3,2-HOPO), or 5-LI(Me-3,2-HOPO) injected into the wound site accelerated clearance of Am(III) from the wound and reduced total body Am(III) significantly more than CaNa 3 -DTPA; the ligands of lesser denticity were not as effective as 3,4,3-LI(1,2-HOPO) (Stradling et al 1993b(Stradling et al , 1995bGray et al 1994;Volf et al 1996a;Stradling 1998).…”

Section: Hydroxypyridinonate Ligandsmentioning

confidence: 99%

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

Durbin¹

2008

Health Physics

106

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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.

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Section: 43-li(12-hopo)mentioning

confidence: 94%

Section: Dfo-(12-hopo)mentioning

confidence: 95%

Section: Catecholate and Hydroxamate Ligandsmentioning

confidence: 97%

Section: Hydroxypyridinonate Ligandsmentioning

confidence: 99%

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

Durbin¹

2008

Health Physics

106

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“…Many chelating agents such as 3,4,3-LIHOPO [19,[34][35][36], Tiron [37,38], ethane-1-hydroxy-1,1-bisphosphonate (EHBP) [39][40][41]46], deferiprone (L1) 1,2-dimethyl-3-hydroxypyrid-4-one [42], DTPA [43], CBMIDA [44] and 1,2-diamino cyclohexyl-tetramethylenetetraphosphonate (CTTP) [45] have been examined for the removal of uranium (Table 4). Although DPTA is often said that it can remove uranium from the body, its effectiveness remains unclear…”

Section: The Use Of Chelating Agents For Minimizing Uranium Body Incomentioning

confidence: 99%

Chelating Agents Used for Plutonium and Uranium Removal in Radiation Emergency Medicine

Fukuda¹

2005

CMC

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The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.

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Beyond Biological Chelation: Coordination of f‐Block Elements by Polyhydroxamate Ligands

Sockwell

Wetzler

2018

Chemistry A European J

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The promise of polyhydroxamic acid ligands for the selective chelation of the f-elements is becoming increasingly more apparent. The initial studies of polyhydroxamic acid siderophores showed the formation of highly stable complexes with Pu(IV), but a higher preference for Fe(III) hindered effective applications. The development of synthetic routes toward highly pure and customizable ligands containing multiple hydroxamic acids allowed for the growth of new classes of compounds. While the first round of these ligands focused on the incorporation of siderophore-like frameworks, the new synthetic strategies led to small molecules of various frameworks and even resins for applications in the field of f-element separations and biological desorption. Unfortunately, a lack of consistent stability constant data makes direct comparisons across this body of work difficult. More studies into the stability constants and separations of the f-elements in a variety of pH ranges is necessary to truly realize the potential for polyhydroxamic acid ligands.

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Early Chelation Therapy for Injected Pu-238 and Am-241 in the Rat: Comparison of 3,4,3-LIHOPO, DFO-HOPO, DTPA-DX, DTPA and DFOA

Cited by 28 publications

References 14 publications

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

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

Chelating Agents Used for Plutonium and Uranium Removal in Radiation Emergency Medicine

Beyond Biological Chelation: Coordination of f‐Block Elements by Polyhydroxamate Ligands

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