Differences in the intracellular processing of the radiolabel following the uptake of iodine-125- and technetium-99m-neogalactosyl albumin by the isolated perfused rat liver.

Neogalactosyl albumin (NGA) is a synthetic ligand to the asialoglycoprotein receptor (hepatic binding protein), which has been proposed as a useful receptor binding radiopharmaceutical for the noninvasive assessment of liver function. We have compared the uptake and intracellular processing of iodine-125- (125I) and technetium-99m- (99mTc) NGA following its administration as a 1-min pulse (147 pmol) to the isolated perfused rat liver. Approximately 40% of a pulse of either 125I- or 99mTc-NGA were taken up first pass by the liver. Of the 125I taken up by the liver, 82% was released after 15-20 min at the sinusoidal pole of the hepatocyte, predominantly as small molecular weight metabolites. A further 8% of the 125I-associated radioactivity was secreted as intact NGA into bile by the non-lysosomal (direct) pathway while 6% remained in the liver 1 hr after the pulse. In contrast, of the 99mTc taken up by the liver, only 4% reappeared in the perfusate while 40% was secreted into bile by the lysosomal (indirect) pathway and 55% remained in the liver 1 hr after the pulse. Since labeled metabolites of 99mTc-NGA do not appear in plasma, this permits kinetic modeling with 99mTc-NGA without correction for labeled metabolites. Thus, 99mTc-NGA is an excellent candidate as a receptor-binding radiopharmaceutical.