The Distribution and Retention of Hexavalent 233 U in the Beagle

Abstract

The distribution, retention, and excretion of 233U were measured in seven beagles injected intravenously with 2.8 /zCi 233U(VI)/kg (-3 mg/dog) in citrate buffer and sacrificed at times ranging from 1 to 726 days postinjection (PI). The concentration of U in plasma decreased rapidly, and for the first 24 hr PI could be described by a triphasic exponential equation with half-times of 0.92, 46, and 315 min. The uranium in the blood at 5 min PI was present as either a protein (transferrin-albumin) or a carbonate/bicarbonate complex. Up to 60% of the injected U was excreted during the first day, most of it in the urine. Whole-body retention was 17% at 7 days, 10% at 94 days, 7.6% at 1 year, and less than 5% at 2 years PI. Except for the kidney, only a small fraction of the injected U was retained in soft tissues. At 1 day PI, the liver contained 1.1% of the injected U and its subcellular distribution was similar to that seen with Pu(IV). At 1 day PI, 7.7% of the U was found in the skeleton; this amount decreased with a biological half-life of 883 days. Initially, U was deposited nonuniformly on bone surfaces with areas of intense hot spots adjacent to areas with intermediate and low concentrations. At later times redistribution and/or diffusion of U into the bone volume produced a deposition pattern intermediate to that of 239Pu (surface) and 226Ra (volume). The heterogeneity of surface deposits persisted, and isolated segments of the trabecular bone showed intense surface deposits at times greater than 1 year PI. Twenty-two percent of the injected U was found in the kidneys at 1 day PI with high concentrations localized in the proximal tubules. The initially high concentration of U in this organ was correlated with extensive diuresis and a persistent elevation in blood urea nitrogen. Damage to proximal tubules was attributed primarily to chemical toxicity but was aggravated by simultaneous a irradiation. It is postulated that the deposition of U on trabecular endosteal surfaces will induce osteosarcoma(s) following prolonged exposure to 233U or 232U.