Biodistribution, with high uptake by the reproductive tract, of an intraperitoneally infused radiohalogenated steroidal estrogen-receptor ligand

Abstract

We infused [ 123]16α-( 123I)-iodo-estradiol ([ 123]E2) intraperitoneally (i.p.) into swine to study its biodistribution and to explore the i.p. use of radiohalogenated steroid estrogen-receptor (ER) ligands as a potential option for diagnosing and treating intra-abdominal, retroperitoneal, and distant sites of advanced ER-rich malignancies. Fifty to 80% of the radiolabel was absorbed from the peritoneal cavity within 30 minutes, and 30 to 50% of the infused radiolabel was excreted in the urine within 2 hr. The rate of biliary clearance was maximal within 25 minutes. At 3 hr, the ER-rich reproductive tract had >63 times the concentration of radiolabel in blood; the former was blocked by non-labeled competitors for ER. Uptake by non-ER-rich tissues, compared to blood, ranged from 0.7:1 (heart and lungs) to 16:1 (spleen); the omentum, however, exhibited a concentration as high as 64:1, which was not blocked by non-labeled ER ligands. Uptake by ER-rich target tissue remained high when charcoal was used to prevent reabsorption of radiolabel from the digestive tract after its biliary excretion, and when the products of biliary excretion were removed by catheterization of the common bile duct. Neither charcoal nor exteriorization of bile appeared to affect urinary clearance of the radiolabel over the time course of the experiments. Taken together with the recent development of syntheses that yield radiohalogenated sex steroid receptor ligands of high specific activity, our findings are encouraging for the potential application of radiolabeled ligands as i.p. administered pharmaceuticals. The advantage of the i.p. route is that it provides direct uptake of the pharmaceutical by free-floating clusters and individual cancer cells in ascitic fluid, as well as delivery via the circulation to vascularized intra- and/or extraperitoneal metastases.