Behavior of [185W]thiotungstates injected into sheep and the influence of copper: their fate and the effect of the compounds upon plasma copper.

[185W]trithio- and tetrathiotungstates (0.5 mg W) were injected intravenously into sheep. The compounds circulated in plasma bound reversibly to plasma proteins, particularly to albumin. After the first few minutes, levels declined exponentially with a T 1/2 of 12-14 hr. The initial movement of [185W]trithiotungstate from the plasma compartment was delayed transiently by the immediate injection of copper (2-6 mg); the longer-term metabolism was unaffected. The final fate of the compounds appeared to be hydrolysis and excretion in urine as [185W]tungstate. 185W from [185W]trithiotungstate appeared more rapidly than from [185W]tetrathiotungstate, but in both the rate was unaffected by copper injections. Since the appearance in urine did not correspond to the disappearance from plasma, it was suggested that the hydrolysis occurred in extravascular tissues and that the liver might be the site. A control experiment showed that [185W]tungstate in plasma was very rapidly cleared (and appeared in urine). At higher W levels (25-50 mg W per sheep per day), systematic copper metabolism was perturbed since plasma copper levels rose. The experiments demonstrated that in sheep the behavior and the effects of thiotungstates and thiomolybdates are sufficiently similar for 185W to be used as a more convenient alternative to 99Mo for longer-term studies on the interaction of the compounds with copper metabolism in animals.