title: Differential receptor targeting of liver cells using 99mTc-neoglycosylated human serum albumins.
abstract: Neolactosyl human serum albumin (LSA) targets asialoglycoprotein receptor and shows high liver uptake due to accumulation in hepatocytes. Although neomannosyl human serum albumin (MSA) also shows high liver uptake, it has been reported to be taken up by Kupffer cells and endothelial cells. We compared the biological properties of LSA and MSA. 99mTc-LSA and 99mTc-MSA biodistribution in mice were investigated after intravenous injection. In vivo localization of rhodaminisothiocyanate (RITC)-LSA and fluoresceineisothiocyanate (FITC)-MSA were investigated in mouse liver. Excretion routes of 99mTc-LSA and 99mTc-MSA metabolites were examined. Both 99mTc-LSA and 99mTc-MSA showed high liver uptakes. RITC-LSA was taken up by hepatocytes whereas FITC-MSA was taken up by Kupffer cells and endothelial cells. 99mTc-MSA showed higher spleen and kidney uptakes than 99mTc-LSA. 99mTc-LSA metabolites excreted in urine and feces accounted for 44.4 and 50.0% of 99mTc-LSA injected, respectively, while 99mTc-MSA metabolites accounted for 51.5 and 10.3%, respectively. In conclusion, LSA is specifically taken up by hepatcytes while MSA by Kupffer cells and endothelial cells. After taken up by the liver, LSA is metabolized by the hepatocytes and then excreted through both the hepatobiliary tract and kidney, whereas MSA is metabolized by Kupffer cells and endoghelial cells and then excreted mainly through the kidney.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Mee Kyung
authors.initials: MK
authors.lastname: Hong
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: D000418:Albumins / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D002352:Carrier Proteins / Q000493:pharmacokinetics*; D019793:Fluorescein / Q000737:chemistry; D022781:Hepatocytes / Q000000981:diagnostic imaging; D006801:Humans; D007553:Isotope Labeling; D007728:Kupffer Cells / Q000000981:diagnostic imaging; D008099:Liver / Q000166:cytology / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects*; D012235:Rhodamines / Q000737:chemistry; D012709:Serum Albumin / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics; D013668:Technetium Tc 99m Aggregated Albumin / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D002352:Carrier Proteins; D019275:Radiopharmaceuticals; D011955:Receptors, Drug; D012235:Rhodamines; D012709:Serum Albumin; D013668:Technetium Tc 99m Aggregated Albumin; C049720:lactosylated serum albumin; C087161:mannosyl-neoglycoalbumin; D013667:Technetium; C027755:rhodamine isothiocyanate; D019793:Fluorescein