Biological Behaviour of Pu Administered to Animals as Pu-Standard LICAM(C) Complex: Therapeutical Attempts to Decrease Pu Kidney Burden

Abstract

<jats:p> The biological fate of plutonium (Pu) introduced as a Pu-standard LICAM(C) complex was investigated in male rats of two strains, in male and female mice and in the baboon. We observed that, whatever the animal species or the entry route, this complex was deposited rapidly in the kidney. In addition, more of the complex accumulated in the rat (16% of injected radioactivity) than in either the mouse (7%) or baboon (5%). This Pu deposit was cleared spontaneously with a half-life of 10 days in the rat and only 5 days in the mouse. We noted that the complex was deposited on bone during this period and that, 10 days after the introduction of Pu, the skeleton became the main organ of retention of Pu (7% of the dose in the rat, 4% in mice and 3% in the baboon). In spite of this, which would indicate that Pu-standard LICAM(C) resembles a weak complex, gut transfer was comparable with that of a strong complex 1.10<jats:sup>-3</jats:sup> ( f1 = 1.10-3) . Pu deposit seemed to be pH dependent and could be modified be varying the pH balance of urine. Bicarbonate was among the most effective of the different drugs used to affect this balance, as 5 h of continuous perfusion decreased the kidney Pu burden by a factor of 4. Such efficacy was also observed with diethylenetriaminepenta-acetic acid (DTPA) perfusion. The pragmatic consequence of these experiments is the recommendation of mixed therapy: standard LICAM(C) plus bicarbonate or DTPA. </jats:p>

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

“…In baboons that inhaled 239 Pu(IV)-TBP, 10 injections of 30 mol kg Ϫ1 of 3,4,3-LICAM(C) in 28 d reduced bone and liver Pu(IV) more than CaNa 3 -DTPA, but neither ligand influenced lung Pu(IV) (Métivier et al 1985b;Volf 1986;Volf et al 1986;Stradling et al 1986Stradling et al , 1989Gérasimo et al 1986).…”

Revue des principales caractéristiques du237Np

“…Les agents chélateurs classiques de décontamination interne sont pratiquement inefficaces envers le neptunium (Morin et al, 1973;Paquet et al, 1994;Thomson, 1982;Volf et al, 1986) et l'utilisation synergique de ces molécules semble souhaitable afin d'éviter un possible effet adverse (Gachalyi et al, 1987;Gachalyi et al, 1989;Gerasimo et al, 1986;Volf et al, 1986).…”

Chelation of 238Pu ( IV ) in Vivo by 3,4,3-LICAM ( C ) Effects of Ligand Methylation and Ph

“…Immediately after Pu-3,4,3-LICAM( C) is introduced into or forms in blood, large amounts of Pu accumulate temporarily in the kidneys in the course of excretion, and most of the Pu is rapidly eliminated in passed urine as the catecholate complex Gerasimo et al (1986). Immediately after Pu-3,4,3-LICAM( C) is introduced into or forms in blood, large amounts of Pu accumulate temporarily in the kidneys in the course of excretion, and most of the Pu is rapidly eliminated in passed urine as the catecholate complex Gerasimo et al (1986).…”

“…respectively) (Stradling et al 1986). In mice and rats that inhaled Pu and were treated once with Euro-LICAM (C) or were given one intratracheal intubation of Pu-Euro-LICAM (C), kidney Pu decreased spontaneously with a half-time of 10-20 d (Stradling et al 1986;Gerasimo et al 1986). or intubated into the lungs (mouse about 4.6% and rat 9.3-1 8.9% ID, compared with 24-h Pu-injected controls, 0.8 1 and 0.4% ID, respectively; Stradling et al 1986;Gerasimo et al 1986).…”

“…Third, Pu deposition in kidneys following treatment with 3,4,3-LICAM(C) was reduced or prevented, and deposited Pu was eliminated faster by alkalizing the urine (Gerasimo et al 1986). Conversely, Pu excretion was reduced in mice by acidifying the blood and urine with NH4Cl.…”