Effects of Ursodeoxycholic Acid on the Biodistribution and Excretion of Various Technetium-99m Radiopharmaceuticals in Rat
Abstract Background In previous studies, ursodeoxycholic acid (UDCA) accelerated the biliary excretion of technetium-99m (Tc-99m) hepatobiliary radiopharmaceutical and increased F-18 fluoro-deoxy-glucose (FDG) excretion from various organs. As an extension of the previous studies, the present study investigated the effect of oral administration of UDCA on the biodistribution and excretion of various Tc-99m labeled radiopharmaceuticals. Materials Sixty rats were randomly assigned to the Control or UDCA groups. Tc-99m HDP, Tc-99m pertechnetate, and Tc-99m DMSA were injected via the tail vein. Thirty min after the injection, the Control group was administered normal saline and the UDCA group was given 5 mg or 10 mg of UDCA orally. Thirty min, and 1, 2, 3, and 4 h after administration of saline or UDCA, images were acquired using a gamma camera. Images were analyzed by drawing a region of interest (ROI) in the relevant organs depending on the type of radiopharmaceutical used. Four imaging parameters, Radioactivity, Rate of change (%), Rate of change by section (%), and Radioactivity/net injection dose (Radioactivity/ID (%)) were compared between groups. To investigate the action of UDCA on radiotracer excretion in the kidneys and from the soft tissues, Tc-99m MAG3 dynamic imaging was performed and Radioactivity and Radioactivity/total body activity (Radioactivity/TBA (%)) of the soft tissue, both kidneys, and the bladder were compared. Results In the image analysis of Tc-99m HDP with 10 mg of UDCA, Radioactivity, and Radioactivity/ID (%) of the buttock was lower in the UDCA group at 4 h (P = 0.019, P = 0.031). Similar effects were also found in the Tc-99m HDP experiments with 5 mg of UDCA. Rate of change (%) of buttock Radioactivity was significantly different at 3 h − 30 min and 4 h − 30 min and buttock Radioactivity in the UDCA group decreased more substantially (P = 0.008, P = 0.024). In the image analysis of Tc-99m pertechnetate, Radioactivity of the buttock was higher in the Control group at 1, 3, and 4 h. Rates of change (%) in the thyroid gland and the buttock were different at 1 h – 30 min, 3 h – 30 min, and 4 h − 30 min and Radioactivity in the UDCA group decreased more substantially. Radioactivity/ID (%) was statistically different in the buttock at 4 h (P = 0.041). In the image analysis of Tc-99m DMSA, Radioactivity of the kidney increased in the UDCA group at 1 h – 30 min, while that in the Control group showed little change. In the analysis of the Tc-99m MAG3 dynamic images, Radioactivity and Radioactivity/TBA (%) of the kidney were significantly higher in the UDCA group at 2 min (P = 0.014, P = 0.035). At 5 and 10 min, Radioactivity/TBA (%) of the soft tissue in the UDCA group was lower than that of the Control group (P = 0.001, P = 0.022). At 20, 25, and 30 min, there was no difference in Radioactivity and Radioactivity/TBA (%) of soft tissue, both kidneys, and the bladder. Conclusion The present study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of Tc-99m labeled radiopharmaceuticals. This investigation could contribute to broadening of the field of pharmacologic application of UDCA.