title: Hepatobiliary handling of iodine-125-Tyr3-octreotide and indium-111-DTPA-D-Phe1-octreotide by isolated perfused rat liver.
abstract: Radiolabeled bioactive peptides may show receptor-mediated binding to tumors, making them suitable for scintigraphic imaging. The liver is an important organ for peptide clearance. To gain insight into the uptake and intracellular processing of somatostatin analogs, we compared the hepatobiliary handling of 125I-Tyr3-octreotide and 111In-DTPA-D-Phe1-octreotide, which are successfully used to image somatostatin receptor-positive tumors in vivo in isolated recirculating perfused rat livers. Sixty minutes following administration of the radiolabeled peptides, perfusion medium and biliary radioactivity were analyzed. Radioiodinated Tyr3-octreotide was rapidly cleared by the liver and 60% of the dose was excreted intact into the bile after 60 min. In contrast, 111In-DTPA-D-Phe1-octreotide was not cleared by the liver; medium radioactivity levels remained about constant and only 2% of the dose was found in the bile. These results are in agreement with in vivo findings in rats and humans. We concluded that isolated rat liver perfusion is a good system to rapidly gain insight into the hepatic handling of radiopharmaceuticals.
authors.affiliation: Department of Nuclear Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: W A
authors.initials: WA
authors.lastname: Breeman
authors.forename: M E
authors.initials: ME
authors.lastname: van der Pluijm
authors.forename: P P
authors.initials: PP
authors.lastname: Kooij
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: R
authors.initials: R
authors.lastname: Docter
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide