Comparative Efficacies of 3,4,3-LIHOPO and DTPA for Enhancing the Excretion of Plutonium and Americium from the Rat After Simulated Wound Contamination as Nitrates

Abstract

With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 238Pu and 241Am from the rat after subcutaneous (s.c.) and intramuscular (i.m.) injection of about 200 Bq of each actinide (0.3 ng Pu, 1.6 ng Am). After the s.c. deposition of 238Pu and 241Am, both ligands were more effective after local administration than (in decreasing order) their repeated interperitoneal (i.p.) injection, single i.p. injection and continuous infusion. Dosages of 3 mumol kg-1 of 3,4,3-LIHOPO were at least as effective as 30 mumol kg-1 DTPA after each mode of administration. The most effective regimen of those investigated for s.c. 238Pu and 241Am involved local administration of 30 mumol kg-1 of 3,4,3-LIHOPO at 30 min followed by i.p. injections at 6 h, 1, 2 and 3 day. By day 7 after exposure, the amounts of 238Pu and 241Am retained in the body were 2 and 7% of those in controls, respectively and 10 and four times less than when DTPA was administered using the same regimen. The ligand 3,4,3-LIHOPO was more effective for 238Pu and 241Am after their i.m. injection. This was attributed to the greater retention of these actinides at the wound site (97 versus 67%) when treatment commenced. After a single local injection of 30 mumol kg-1 at 30 min, the amounts of 238Pu and 241Am retained in the body at 7 day were 0.9 and 0.8% of controls. These values were 34 and 27 times less than after local and repeated i.p. injections of DTPA at dosages of 30 mumol kg-1. It is concluded that the administration of 3,4,3-LIHOPO represents potentially a most significant advance in the treatment of wound contamination by 238Pu and 241Am by chelating agents.

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

“…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). Rats were injected im with mixed oxide (MOX) particles, and 3,4,3-LI(1,2-HOPO) was repeatedly injected into the wound site.…”

“…Reductions of those actinides in the wound site, skeleton and soft tissues by 3,4,3-LI(1,2-HOPO) were appreciably greater than by CaNa 3 -DTPA in all treatment protocols. In the same dosage regimens (30 mol kg Ϫ1 once or five times in 3 d) the HOPO ligand removed 99% of 238 Pu(IV) (molar ratio 5 ϫ 10 6 ) from the wound site and tissues and 95% of a substantially larger mass of 239 Pu(IV) (molar ratio 8 ϫ 10 3 ) (Stradling et al 1993b(Stradling et al , 1995aGray et al 1994;Volf et al 1996a;Paquet et al 1995aPaquet et al , 2003.…”

Functional Sorbents for Selective Capture of Plutonium, Americium, Uranium, and Thorium in Blood

“…It is not surprising that HOPO ligands are most effective for these actinides than other ligands. The Raymond group has evaluated liquid formulations of HOPO ligands in rodent models and found them to be highly effective for facilitating the excretion of absorbed Th, Am, and Pu (Stradling et al 1993, Stradling and Moody 1995, Volf et al 1996). …”

“…The diethylenetriamine pentaacetate (DTPA) recommended for thorium is still ineffective in animal studies at high doses (Stradling et al 1991). Although DTPA has been reported to be effective for plutonium and americium, emerging ligands that are significantly more effective for plutonium and americium decorporation in animals have been reported (Stradling et al 1993, Volf et al 1996). …”

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

“… Structures of polyHA small molecules. (I) EDTA‐DX, (II) EDTPHA, (III) DHA, (IV) no abbreviation given, (V) no abbreviation given, (VI) H 4 CDTMAHA, (VII) CYTROX, (VIII) 3,4,3‐LI(1,2‐HOPO), (IX) Calix(HYD) 4 , (X) TAM(HOPO) 2 , (XI) BAMPTH, (XII) no abbreviation given …”