ACTION OF DTPA ON HEPATIC PLUTONIUM .3. EVIDENCE FOR A DIRECT CHELATION MECHANISM FOR DTPA-INDUCED EXCRETION OF MONOMERIC PLUTONIUM INTO RAT BILE

Na3 Ca diethylenetriaminepenta[2-14C]acetic acid ([14C]DTPA, 0.25 mmol/kg, 0.210 mCi/mmol) was administered via the jugular vein to 3 rats whose bile ducts and urinary bladders were cannulated. Bile and urine were collected for 24 h after injection and tissues and excreta were analyzed for 14C content. [14C]DTPA was identified in the bile samples by cochromatography with unlabeled DTPA on an anion-exchange column system. The existence of a minor excretion pathway was demonstrated for DTPA into rat bile, accounting for 0.12% of the injected dose by 24 h after administration. Bile was collected for 24 h following the administration of unlabeled Na3[CaDTPA] (0.25 mmol/kg i.v.) to a rat receiving 239Pu(IV)citrate (5.7 .mu.Ci/kg i.v.) 24 h prior to DTPA. Bile samples containing Pu were analyzed using anion-exchange column chromatography. Of the Pu present in bile chromatographed 80-90% had a single peak in the position of the Pu-DTPA complex. Cochromatography of the 0-6 h bile sample with a 239Pu-[14C]DTPA complex revealed the Pu appearing in bile following DTPA treatment comigrated with the 239Pu-[14C]DTPA complex. In the rat DTPA apparently acts to remove hepatic deposits of monomeric Pu by formation of the Pu-DTPA complex followed by excretion of the complex into bile.