title: 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.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Royal Liverpool Hospital, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Gore
authors.forename: A I
authors.initials: AI
authors.lastname: Morris
authors.forename: I T
authors.initials: IT
authors.lastname: Gilmore
authors.forename: P J
authors.initials: PJ
authors.lastname: Maltby
authors.forename: J R
authors.initials: JR
authors.lastname: Thornback
authors.forename: D
authors.initials: D
authors.lastname: Billington
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013667:Technetium / Q000493:pharmacokinetics
chemical_list: D000418:Albumins; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; C036586:technetium Tc 99m neogalactoalbumin; D013667:Technetium