technetium-tc-99m-lidofenin and 23-seleno-25-homotaurocholic-acid

In an experimental study on 65 rats the influence of different Roux-Y biliary anastomoses on the enterohepatic bile acid circulation was investigated. Long (10 cm) and short (3 cm) isoperistaltic and long (10 cm) anisoperistaltic Roux-Y loops were studied and compared to sham-operated controls. 75-SeHCAT a y-labeled synthetic bile acid was used for assessment of enterohepatic circulation. Hepatic excretion and enteric bile flow was investigated by 99m-Tc-HIDA. Intestinal transit time was evaluated by 51-Cr-EDTA an inert marker of intestinal contents. Animals with biliary anastomoses showed an increased retention of the synthetic bile acid 75-SeHCAT compared to the controls. Highest retention values were found in animals with anisoperistaltic loops (t1/2 = 98.6 h). Isoperistaltic loops showed uniform values independently of the length of the Roux-limb (t1/2 = 59.8 h resp. 59.3 h). Differences to the controls (t1/2 = 42.6 h) were highly significant (p less than 0.001). In the 99m-Tc-HIDA hepatic excretion into the connected small bowel was normal in all groups. But in rats with biliary anastomoses a marked stasis of the 99m-Tc-HIDA in the Roux-Y loop was apparent. Bowel transit time tested by 51-Cr-EDTA showed comparable results in all groups without significant differences. The results demonstrate an increased bile acid retention in Roux-Y biliary anastomoses. An alteration of the enterohepatic circulation due to stasis in the Roux-Y limb seems to be the underlying mechanism.

Topics: Anastomosis, Roux-en-Y; Animals; Bile Acids and Salts; Choledochostomy; Chromium Radioisotopes; Edetic Acid; Enterohepatic Circulation; Imino Acids; Male; Organotechnetium Compounds; Peristalsis; Postoperative Complications; Radionuclide Imaging; Rats; Taurocholic Acid; Technetium Tc 99m Lidofenin

75Se-homocholic acid-taurine (75SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [14C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75SeHCAT (14.3% and 1.5% dose/min) than for [14C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (275 vs. 670 ml/min). In vitro, 75SeHCAT was bound to serum proteins more completely than [14C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [14C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75SeHCAT in assessing liver disease should be investigated.

Topics: Adult; Aged; Carbon Radioisotopes; Female; Humans; Imino Acids; Liver; Male; Middle Aged; Organometallic Compounds; Taurocholic Acid; Technetium Tc 99m Lidofenin